JP6464659B2 - (Meth) acryloyloxyadamantanecarboxylic acid compound and method for producing the same - Google Patents

Description

  The present invention has an adamantane skeleton and is useful as an intermediate for medicines and agricultural chemicals, optical materials such as optical fibers, optical waveguides, optical disk substrates, and photoresists, functional resin materials excellent in heat resistance, surface hardness, etc., and other various industrial products (Meth) acryloyloxyadamantane (related to a method for producing a carboxylic acid compound)

  An alicyclic compound having a bridgehead position such as an adamantane skeleton has structurally rigid properties, high heat resistance, and excellent optical properties. Etc. (Patent Documents 1 to 3). Among them, a (meth) acryloyloxyadamantanecarboxylic acid compound having a (meth) acryloyl group and a carboxyl group in the same molecule can be obtained by introducing a substituent having a different reactivity from the (meth) acryloyl group onto the carboxyl group ( The functionality of the (meth) acryloyl polymer can be increased and is useful.

  Several synthetic routes are known as a method for introducing a (meth) acryloyl group and a carboxyl group. Patent Document 4 describes a method of esterifying a hydroxyadamantanecarboxylic acid compound by reacting (meth) acrylic acid under heating conditions in the presence of an acid catalyst. Patent Document 5 describes hydroxyadamantanecarboxylic acid. A method of reacting a compound with (meth) acrylic acid chloride is described.

JP 2007-211208 A JP 2012-246246 A Japanese Patent Laid-Open No. 4-39665 JP 2011-37953 A JP 2001-240625 A

However, the present inventors have found that although it is possible to obtain a (meth) acryloyloxyadamantanecarboxylic acid compound by the known synthesis route described above, it is difficult to obtain a high purity.
That is, in the route described in Patent Document 4, it is difficult to remove the by-product in which the condensation reaction between the hydroxyl group and the carboxyl group of the hydroxyadamantanecarboxylic acid compound has progressed. In the route described in Patent Document 5, ) It is difficult to remove (meth) acrylic acid produced by hydrolysis of acrylic acid chloride.
This invention is made | formed in view of the said problem, and it aims at providing the method etc. which manufacture a highly purified (meth) acryloyloxyadamantane carboxylic acid compound.

As a result of intensive studies, the present inventors have found a method for producing a (meth) acryloyloxyadamantanecarboxylic acid compound represented by the general formula (1) with high purity by the following steps (1), (2) and (3). The headline, the present invention has been reached.
Step 1: a step of reacting a compound represented by formula (2) with a halogenated methyl alkyl ether represented by formula (3) to protect a carboxyl group to obtain a compound represented by formula (4) .
Step 2: A step of adding (meth) acrylic acid chloride to the reaction solution of Step 1 to convert the hydroxyl group to (meth) acrylic ester to obtain a compound represented by the formula (5).
Process 3: The process of producing | generating the compound represented by Formula (1) by deprotecting the protective group of the carboxyl group which the compound represented by Formula (5) has.
(In the formula, R ¹ is bonded to carbons other than the bridge head position, each independently represents hydrogen or an alkyl group having 1 to 6 carbon atoms, and m = 12. R ² represents n COOH, p And q alkyl groups having 1 to 6 carbon atoms, n, p and q are natural numbers having a relationship of n = 1 to 3 and n + p + q = 3, and R ³ represents a hydrogen or methyl group. Show.)
(In the formula, R ¹ and R ² have the same meanings as in formula (1).)
(In the formula, X is a halogen, and the substituent R ⁴ represents an alkyl group having 1 to 12 carbon atoms.)
(In the formula, R ⁵ represents n COOCH ₂ OR ⁴ _, p hydrogen and q alkyl group having 1 to 6 carbon atoms. R ¹ , m, n, p and q are represented by the formula (2). And R ⁴ is synonymous with formula (3).
(In the formula, R ¹ and R ³ have the same meaning as in formula (1), and R ⁵ has the same meaning as in formula (4).)

  2. 1. X in the formula (3) is chlorine; A method for producing a compound represented by the formula (1) described in 1.

  3. 1. the halogenated methyl alkyl ether is chloromethyl methyl ether; A method for producing a compound represented by the formula (1) described in 1.

  4). The reaction of the step 2 is performed in a halogen solvent. ~ 3. The manufacturing method of the compound represented by Formula (1) as described in any one of these.

  5. The deprotection reaction in Step 3 is a reaction of water and the compound represented by the formula (5) in the presence of an acidic catalyst. ~ 4. The manufacturing method of the compound represented by Formula (1) as described in any one of these.

  6.1. ~ 5. The compound represented by the formula (1) obtained by the production method described in any one of the above is washed with an alkali, neutralized and extracted as a salt in an aqueous layer, and then an acidic compound is added. A compound represented by formula (1) obtained by crystallization separation.

  7). 5. The alkali used for the alkali cleaning is sodium hydrogen carbonate. The compound represented by Formula (1) as described in.

  8). 5. The acidic compound is phosphoric acid Or 7. The compound represented by Formula (1) as described in.

  9. 5. After adding an acidic compound, further by adding a solvent and activated carbon to remove by-products, then distilling off the solvent of the solution, and further adding a poor solvent to perform crystallization separation. ~ 8. The compound represented by Formula (1) as described in any one of these.

  10. After adding a solvent and activated carbon to the compound represented by the formula (1) obtained by crystallization separation performed after the alkali washing to remove by-products, the solvent of the solution is distilled off, and a poor solvent is added. 5. obtained by performing crystallization separation. ~ 8. The compound represented by Formula (1) as described in any one of these.

  11. 8. The solvent added with the activated carbon contains an aliphatic hydrocarbon solvent. Or 10. The compound represented by Formula (1) as described in.

  12 8. The high molecular weight component in the compound represented by the formula (1) is GPC-UV 1.0% or less and GPC-RI 1.0% or less. ~ 11. The compound represented by Formula (1) obtained by the purification method as described in any one of these.

  INDUSTRIAL APPLICABILITY According to the present invention, it is useful as a pharmaceutical / agrochemical intermediate, an optical material such as an optical fiber, an optical waveguide, an optical disk substrate, a photoresist, a functional resin material excellent in heat resistance, surface hardness, and other various industrial products (meta). Provided is a method for producing an acryloyloxyadamantanecarboxylic acid compound with high purity.

The present invention relates to a method for producing a high-purity (meth) acryloyloxyadamantanecarboxylic acid comprising steps 1 to 3 and the like.
Step 1: A hydroxyadamantanecarboxylic acid compound represented by the formula (2) is reacted with a halogenated methyl alkyl ether represented by the formula (3) to protect the carboxyl group, which is represented by the formula (4). The process which makes a compound.
Step 2: A step of adding (meth) acrylic acid chloride to the reaction solution of Step 1 to convert the hydroxyl group to (meth) acrylic ester to obtain a compound represented by the formula (5).
Process 3: The process of obtaining the (meth) acryloyl compound represented by Formula (1) by deprotecting the protective group of the carboxyl group which the compound represented by Formula (5) has.
Hereinafter, embodiments of the present invention will be described in detail.

  Step 1 is a step in which the carboxyl group of the hydroxyadamantanecarboxylic acid compound is protected using a halogenated methyl alkyl ether.

The hydroxyadamantanecarboxylic acid compound used as a raw material in Step 1 of the present invention is an adamantane compound having a hydroxyl group and a carboxyl group represented by the formula (2).
Carbon other than the bridge head position has hydrogen or an alkyl group having 1 to 6 carbon atoms as the substituent R ¹ . R ¹ binds to a carbon other than a bridge head position, each independently, represent hydrogen or an alkyl group having 1 to 6 carbon atoms, m = 12. R ² represents n COOH, p hydrogen, and q 1 to 6 alkyl groups, and n, p, and q are natural numbers in a relationship of n = 1 to 3 and n + p + q = 3. It is.

Specific examples of the hydroxyadamantanecarboxylic acid compound include 3-hydroxyadamantane-1-carboxylic acid, 3-hydroxy-5-methyl-adamantane-1-carboxylic acid, and 5-ethyl-3-hydroxyadamantane-1-carboxylic acid. Acid, 3-hydroxy-5-propyladamantane-1-carboxylic acid, 3-hydroxy-5,7-dimethyladamantane-1-carboxylic acid, 5,7-diethyl-3-hydroxyadamantane-1-carboxylic acid, and 3 -Hydroxyadamantane monocarboxylic acid compounds such as hydroxy-5,7-dipropyladamantane-1-carboxylic acid, 5-hydroxyadamantane-1,3-dicarboxylic acid, 5-hydroxy-7-methyl-adamantane-1,3- Dicarboxylic acid, 7-ethyl-5-hydroxyadamanta -1,3-dicarboxylic acid, hydroxyadamantane dicarboxylic acid compounds such as 5-hydroxy-7-propyl-adamantane-1,3-dicarboxylic acid, and hydroxyadamantanes such as 7-hydroxyadamantane-1,3,5-tricarboxylic acid Examples of these compounds include those synthesized according to known methods, and commercially available products may be used. Examples of commercially available products include Tokyo Chemical Industry Co., Ltd. products.

In the step 1, the halogenated methyl alkyl ether used for the carboxyl group protecting reaction is a compound represented by the formula (3). For example, fluoromethyl methyl ether, fluoromethyl ethyl ether, fluoromethyl propyl ether, fluoromethyl butyl ether, fluoromethyl pentyl ether, fluoromethyl hexyl ether, chloromethyl methyl ether, chloromethyl ethyl ether, chloromethyl propyl ether, chloromethyl butyl ether, Chloromethyl pentyl ether, chloromethyl hexyl ether, bromomethyl methyl ether, bromomethyl ethyl ether, bromomethyl propyl ether, bromomethyl butyl ether, bromomethyl pentyl ether, bromomethyl hexyl ether, iodomethyl methyl ether, iodomethyl ethyl ether, iodo Methyl propyl ether, iodomethyl butyl ether, iodomethyl Pentyl ether, and iodo-methylhexyl ether, and the like.
These halogenated methyl alkyl ethers may be used in combination of two or more. Among these halogenated methyl alkyl ethers, those in which the halogen is chlorine are preferred, and chloromethyl methyl ether is particularly preferred because it is inexpensive and easy to handle.
As the halogenated methyl alkyl ether, one synthesized according to a known method may be used, or a commercially available product may be used. Examples of commercially available products include Tokyo Chemical Industry Co., Ltd. products.

  The amount of the halogenated methyl alkyl ether used in Step 1 is 0.5 to 1.5 moles, preferably 0.8 to 1.2 moles, relative to the number of moles of the carboxyl group of the hydroxyadamantanecarboxylic acid compound. More preferably, it is 0.9 to 1.1 mole times. Within this range, for example, the carboxyl group protection reaction proceeds sufficiently, and the side reaction in which the hydroxyl group is protected by an excessive amount of the halogenated methyl alkyl ether is suppressed, and the hydroxy group represented by the general formula (4) is suppressed. A decrease in the yield of the adamantane compound can be suppressed.

In the carboxyl group-protecting reaction in Step 1, a base catalyst can be used. Examples of the compound that can be used as a catalyst include amines, and specifically, tertiary amines such as trimethylamine, triethylamine, tripropylamine, diisopropylethylamine, tributylamine, tripentylamine, and trihexylamine. An aliphatic amine having an aromatic ring such as N, N-dimethylaniline, phenyldimethylamine, diphenylmethylamine, and triphenylamine; a cyclic aliphatic such as 1-methylpyrrolidine, 1-methylpiperidine, and 4-methylmorpholine Amines; Amidines such as 1,8-diazabicyclo [5.4.0] -7-undecene and 1,5-diazabicyclo [4.3.0] -5-nonene; Guanidine, 1,1,3,3 -Tetramethylguanidine and 1,2,3-triphenylgua Guanidines such as ninjin; aromatics such as 1-methylpyrrole, pyridine, 2-methylpyridine, 3-methylpyridine, 4-methylpyridine, 2,6-dimethylpyridine, and N, N-dimethyl-5-aminopyridine Examples of amines include quaternary ammonium salts such as tetramethylammonium hydroxide and tetraethylammonium hydroxide.
These can be used individually by 1 type or in mixture of 2 or more types.
A catalyst synthesized according to a known method may be used, or a commercial product may be used. Examples of commercially available products include Wako Pure Chemical Industries, Ltd. and Kanto Chemical Co., Ltd. products, and triethylamine is preferred because it is inexpensive.

  The usage-amount of the base catalyst in the process 1 is 0.8-10.0 mol times with respect to the usage-amount of halogenated methyl alkyl ether, Preferably it is 0.9-5.0 mol times, More preferably, it is 1.0- It is preferable to make it 3.0 mole times. Within this range, the hydrohalic acid produced from the halogenated methyl alkyl ether can be sufficiently neutralized, and the deprotection reaction of the protecting group of the carboxyl group occurring under acidic conditions can be suppressed.

  In step 1, the mixing conditions in the reaction are not limited, but the reaction is generally performed on the reaction solution in which the hydroxyadamantanecarboxylic acid compound represented by the general formula (2), the base catalyst, and a solvent are further mixed in advance. It is preferable to add a halogenated methyl alkyl ether represented by the formula (3). In this order, since the carboxyl group is always present in the reaction solution, the protection reaction of the carboxyl group proceeds selectively, and the generation of by-products having a structure in which the protecting group is also introduced into the hydroxyl group is small. It is to become. The addition method of halogenated methyl alkyl ether may be dripped after dissolving in a solvent, or may be added without a solvent.

In the protection reaction of the hydroxyadamantanecarboxylic acid compound represented by the general formula (2) in Step 1 and the halogenated methyl alkyl ether represented by the general formula (3), a solvent may be used.
Solvents that can be used are diethyl ether, diisopropyl ether, methyl-t-butyl ether, cyclopentyl methyl ether, tetrahydrofuran, dioxane, acetonitrile, benzene, toluene, xylene, methicylene, pseudocumene, chloroform, chlorobenzene, 1,2-dichloroethane, Examples include dichloromethane, acetone, methyl ethyl ketone, methyl isobutyl ketone, dimethylacetamide, dimethylformamide, and dimethyl sulfoxide, and ether solvents such as diethyl ether, diisopropyl ether, methyl-t-butyl ether, cyclopentyl methyl ether, tetrahydrofuran, and dioxane. This is preferable because the progress of the protection reaction is improved.
When the solvent is used, the amount used is 0.1 to 50 times by mass and preferably 0.5 to 20 times by mass with respect to 100 parts by mass of the raw material hydroxyadamantanecarboxylic acid compound.

  Although the specific reaction temperature and reaction time of the said process 1 depend on a substrate concentration and the catalyst to be used, reaction temperature is -20 degreeC-100 degreeC, Preferably it is -10 degreeC-50 degreeC, More preferably, it is 0 degreeC-40. ° C. The reaction time is 0.5 hour to 10 hours, preferably 1 hour to 5 hours, and the pressure is normal pressure, reduced pressure or increased pressure. In addition, the reaction can be performed by appropriately selecting a known method such as a batch system, a semi-batch system, or a continuous system.

  In step 1, a polymerization inhibitor may be added. The polymerization inhibitor is not particularly limited as long as it is a general one. For example, 2,2,6,6-tetramethyl-4-hydroxypiperidine-1-oxyl, N-nitrosophenylhydroxylamine ammonium salt, N-nitrosophenylhydroxylamine aluminum salt, N-nitroso-N- (1-naphthyl) Hydroxylamine ammonium salt, N-nitrosodiphenylamine, N-nitroso-N-methylaniline, nitrosonaphthol, p-nitrosophenol, N, N'-dimethyl-p-nitrosoaniline and other nitroso compounds, phenothiazine, methylene blue, 2-mercapto Sulfur-containing compounds such as benzimidazole, amines such as N, N′-diphenyl-p-phenylenediamine, N-phenyl-N′-isopropyl-p-phenylenediamine, 4-hydroxydiphenylamine, aminophenol Quinones such as hydroxyquinoline, hydroquinone, methylhydroquinone, p-benzoquinone, hydroquinone monomethyl ether, p-methoxyphenol, 2,4-dimethyl-6-t-butylphenol, catechol, 3-s-butylcatechol, 2,2- Examples thereof include phenols such as methylene bis- (6-t-butyl-4-methylphenol), imides such as N-hydroxyphthalimide, oximes such as cyclohexane oxime and p-quinone dioxime, and dialkylthiodipropinates. The addition amount is 0.000001 to 5 times by mass, preferably 0.00001 to 1 by mass, with respect to 100 parts by mass of the compound having a (meth) acryl group.

Next, step 2 will be described in detail.
Step 2 is a step in which the hydroxyl group of the compound represented by formula (4) is (meth) acrylic esterified using (meth) acrylic acid chloride.

In step 2, the reaction solution for the protection reaction obtained in step 1 is used as it is (without a quench / purification operation) (one-pot reaction).
By performing the reaction in one pot, the process can be simplified. Moreover, since the liquid separation operation using the water normally used by quenching or refinement | purification operation can be abbreviate | omitted, the inflow of the water | moisture content to a reaction solution can be suppressed, and the hydrolysis reaction of (meth) acrylic acid chloride can be suppressed.

Examples of the (meth) acrylic acid chloride include methacrylic acid chloride and acrylic acid chloride.
These may be synthesized according to known methods or commercially available products may be used. Examples of commercially available products include those manufactured by Tokyo Chemical Industry Co., Ltd., and methacryloyl chloride is preferred because of its availability.

  The amount of (meth) acrylic acid chloride used in Step 2 is 0.5 to 10 moles, preferably 0, based on the number of moles of the hydroxyl group of the hydroxyadamantane compound represented by the general formula (2) used as a raw material. .8 to 5.0 mole times, more preferably 1.0 to 3.0 mole times. Within this range, the (meth) acrylic esterification reaction proceeds sufficiently, and the amount of methacrylic acid by-produced from (meth) acrylic acid chloride is reduced, facilitating the purification operation.

  In the (meth) acryl esterification reaction in Step 2, a base catalyst can be used. Examples of the catalyst that can be used include amines, specifically, tertiary amines such as trimethylamine, triethylamine, tripropylamine, diisopropylethylamine, tributylamine, tripentylamine, and trihexylamine; N, N -Aliphatic amines having an aromatic ring such as dimethylaniline, phenyldimethylamine, diphenylmethylamine and triphenylamine; cyclic aliphatic amines such as 1-methylpyrrolidine, 1-methylpiperidine and 4-methylmorpholine; 1 Amidines such as 1,8-diazabicyclo [5.4.0] -7-undecene and 1,5-diazabicyclo [4.3.0] -5-nonene; guanidine, 1,1,3,3-tetramethylguanine And guanidi such as 1,2,3-triphenylguanidine Aromatic amines such as 1-methylpyrrole, pyridine, 2-methylpyridine, 3-methylpyridine, 4-methylpyridine, 2,6-dimethylpyridine, and N, N-dimethyl-5-aminopyridine; And quaternary ammonium salts such as methylammonium hydroxide and tetraethylammonium hydroxide. These can be used individually by 1 type or in mixture of 2 or more types.

  The amount to be added is 0.8 to 10.0 mol times, preferably 0.9 to 5.0 mol times, more preferably 1.0 to 3.0 mol times the amount of (meth) acrylic acid chloride used. It is preferable to double. Within this range, for example, hydrohalic acid produced from (meth) acrylic acid chloride is sufficiently neutralized, and under acidic conditions, deprotection reaction for carboxyl group, hydrolysis reaction of (meth) acrylic ester Progress can be suppressed.

  The catalyst may be added at the start of the (meth) acrylic esterification reaction in Step 2, but when the same catalyst as in Step 1 is used, an amount necessary for Step 2 can also be added in Step 1. The method of adding in advance is preferable because the operation in step 2 can be simplified.

  Since Step 2 is a one-pot reaction from Step 1, Step 2 is advanced by adding an acid chloride and, if necessary, a solvent or a base catalyst to the reaction solution obtained in Step 1. The order of adding these to the reaction solution in Step 1 is not particularly limited, but it is preferable to add them in the order of the solvent, the base catalyst, and (meth) acrylic acid chloride. Moreover, it is preferable to inject (meth) acrylic acid chloride into the system while dropping. In this procedure, the hydrohalic acid produced from (meth) acrylic acid chloride is sufficiently neutralized with a base catalyst, and under acidic conditions, deprotection reaction for carboxyl group, hydrolysis reaction of (meth) acrylic ester This is because the progress can be suppressed.

  Since Step 2 is a one-pot reaction from Step 1, the solvent used in Step 1 is usually used. Moreover, in order to make a solvent into the appropriate quantity in the process 2, it can also be added before the process 2. When a solvent is added, the solvent used in Step 1 is used as the solvent to be added, but other solvents can also be added. Solvents that can be added include diethyl ether, diisopropyl ether, methyl-t-butyl ether, cyclopentyl methyl ether, tetrahydrofuran, dioxane, acetonitrile, benzene, toluene, xylene, methicylene, pseudocumene, chloroform, chlorobenzene, 1,2-dichloroethane, Examples include dichloromethane, acetone, methyl ethyl ketone, methyl isobutyl ketone, dimethylacetamide, dimethylformamide, dimethyl sulfoxide and the like. A halogen solvent such as chloroform, chlorobenzene, 1,2-dichloroethane, dichloromethane or the like is preferable because the (meth) acryl esterification reaction proceeds sufficiently when used.

  Although the specific reaction temperature and reaction time of the said process 2 depend on a substrate concentration and the catalyst to be used, generally reaction temperature is 0 degreeC-200 degreeC, Preferably it is 10 degreeC-100 degreeC, More preferably, it is 20 degreeC-80 degreeC. The reaction time can be 0.5 ° C. to 50 hours, preferably 1 hour to 25 hours, and the pressure can be normal pressure, reduced pressure or increased pressure. In addition, the reaction can be performed by appropriately selecting a known method such as a batch system, a semi-batch system, or a continuous system.

  Further, a polymerization inhibitor may be added in Step 2, and there is no particular limitation as long as the polymerization inhibitor is a general one. For example, 2,2,6,6-tetramethyl-4-hydroxypiperidine-1-oxyl, N-nitrosophenylhydroxylamine ammonium salt, N-nitrosophenylhydroxylamine aluminum salt, N-nitroso-N- (1-naphthyl) Hydroxylamine ammonium salt, N-nitrosodiphenylamine, N-nitroso-N-methylaniline, nitrosonaphthol, p-nitrosophenol, N, N'-dimethyl-p-nitrosoaniline and other nitroso compounds, phenothiazine, methylene blue, 2-mercapto Sulfur-containing compounds such as benzimidazole, amines such as N, N′-diphenyl-p-phenylenediamine, N-phenyl-N′-isopropyl-p-phenylenediamine, 4-hydroxydiphenylamine, aminophenol Quinones such as hydroxyquinoline, hydroquinone, methylhydroquinone, p-benzoquinone, hydroquinone monomethyl ether, p-methoxyphenol, 2,4-dimethyl-6-t-butylphenol, catechol, 3-s-butylcatechol, 2,2- Examples thereof include phenols such as methylene bis- (6-t-butyl-4-methylphenol), imides such as N-hydroxyphthalimide, oximes such as cyclohexane oxime and p-quinone dioxime, and dialkylthiodipropinates. The addition amount is 0.000001 to 5 times by mass, preferably 0.00001 to 1 by mass, with respect to 100 parts by mass of the compound having a (meth) acryl group.

  The polymerization inhibitor may be added at the start of the (meth) acrylic esterification reaction in Step 2, but when using the same polymerization inhibitor as in Step 1, the amount required for Step 2 is also added in Step 1. can do. The method of adding in advance is preferable because the operation in step 2 can be simplified.

In the present invention, the (meth) acrylic acid ester compound represented by the general formula (5) obtained after Step 2 can be purified. As a purification method, it can be isolated and purified by a separation / purification method such as washing with water, filtration, concentration, distillation, extraction and the like, or a combination of these methods. For example, a method of washing the reaction solution with water is preferable because additives such as excess halogenated methyl alkyl ether, (meth) acrylic acid chloride, and catalyst are removed.
At this time, the washing water may contain an inorganic salt such as sodium chloride, sodium hydrogen carbonate, sodium carbonate, etc., and may be washed with an alkali such as a sodium hydroxide aqueous solution. In the washing, an organic solvent or the like may be added, and it is usually preferable to use a solvent having a small polarity that can be separated from water. The (meth) acrylic acid ester compound represented by the general formula (5) can be used for the deprotection reaction of the protecting group on the carboxyl group in the previous step 3 after performing the separation and production operation, distilling off the solvent. .

Next, step 3 will be described in detail.
Step 3 is a step of deprotecting the carboxyl group of the (meth) acryloyloxyadamantane compound represented by the general formula (5).

  In step 3, the (meth) acryloyloxyadamantane compound represented by the general formula (5) obtained in step 2 is hydrolyzed in the presence of an acidic catalyst to deprotect the carboxyl group.

  Examples of the acidic catalyst used in Step 3 include inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, and phosphoric acid, formic acid, acetic acid, propionic acid, trifluoroacetic acid, methanesulfonic acid, ethanesulfonic acid, propanesulfonic acid, Examples thereof include organic acids such as fluoromethylsulfonic acid and p-toluenesulfonic acid. Hydrochloric acid and sulfuric acid are preferable because they have a pH sufficient for carrying out the deprotection reaction and can be procured at low cost. These can be used individually by 1 type or in mixture of 2 or more types.

  The usage-amount of an acidic catalyst is 0.01-10 mol times with respect to the mole number of the carboxyl group of the hydroxyadamantane compound represented by General formula (2) used as a raw material, Preferably it is 0.1-5.0 mol. It is preferable to double. Within this range, the deprotection reaction of the carboxyl group can sufficiently proceed. These acidic catalysts may use commercially available products. Examples of commercially available products include 1.0 mol / L hydrochloric acid manufactured by Wako Pure Chemical Industries, Ltd.

  A solvent can be used in the deprotection reaction of Step 3, and the solvents that can be used are methanol, ethanol, propanol, isopropanol, butanol, pentanol, hexanol, diethyl ether, diisopropyl ether, methyl-t-butyl ether, cyclopentyl. Methyl ether, tetrahydrofuran, dioxane, acetonitrile, benzene, toluene, xylene, methicylene, pseudocumene, chloroform, chlorobenzene, 1,2-dichloroethane, dichloromethane, acetone, methyl ethyl ketone, methyl isobutyl ketone, dimethylacetamide, dimethylformamide, dimethylsulfoxide, etc. Preferably, methanol, ethanol, propanol, isopropano having high affinity with water Polar solvents such as benzene, butanol, pentanol, hexanol, diethyl ether, diisopropyl ether, methyl-t-butyl ether, cyclopentyl methyl ether, tetrahydrofuran, dioxane, acetonitrile, acetone, methyl ethyl ketone, dimethylacetamide, dimethylformamide, and dimethylsulfoxide; Preferred are methanol, ethanol, propanol, isopropanol, tetrahydrofuran, dioxane, acetonitrile, acetone, methyl ethyl ketone, dimethylacetamide, dimethylformamide, dimethyl sulfoxide, and the like, and solvents showing miscibility are preferred.

  Although the specific reaction temperature and reaction time of the said process 3 depend on a substrate concentration and the catalyst to be used, generally reaction temperature is 0 to 200 degreeC, Preferably it is 10 to 100 degreeC, More preferably, it is 20 to 80 degreeC. The reaction time can be 0.5 ° C. to 50 hours, preferably 1 hour to 25 hours, and the pressure can be normal pressure, reduced pressure or increased pressure. In addition, the reaction can be performed by appropriately selecting a known method such as a batch system, a semi-batch system, or a continuous system.

  In addition, a polymerization inhibitor may be added to the series of reactions, and the polymerization inhibitor is not particularly limited as long as it is a general one. For example, 2,2,6,6-tetramethyl-4-hydroxypiperidine-1-oxyl, N-nitrosophenylhydroxylamine ammonium salt, N-nitrosophenylhydroxylamine aluminum salt, N-nitroso-N- (1-naphthyl) Hydroxylamine ammonium salt, N-nitrosodiphenylamine, N-nitroso-N-methylaniline, nitrosonaphthol, p-nitrosophenol, N, N'-dimethyl-p-nitrosoaniline and other nitroso compounds, phenothiazine, methylene blue, 2-mercapto Sulfur-containing compounds such as benzimidazole, amines such as N, N′-diphenyl-p-phenylenediamine, N-phenyl-N′-isopropyl-p-phenylenediamine, 4-hydroxydiphenylamine, aminophenol Quinones such as hydroxyquinoline, hydroquinone, methylhydroquinone, p-benzoquinone, hydroquinone monomethyl ether, p-methoxyphenol, 2,4-dimethyl-6-t-butylphenol, catechol, 3-s-butylcatechol, 2,2- Examples thereof include phenols such as methylene bis- (6-t-butyl-4-methylphenol), imides such as N-hydroxyphthalimide, oximes such as cyclohexane oxime and p-quinone dioxime, and dialkylthiodipropinates. The addition amount is 0.000001 to 5 times by mass, preferably 0.00001 to 1 by mass, with respect to 100 parts by mass of the compound having a (meth) acryl group.

In the present invention, the (meth) acryloyloxyadamantanecarboxylic acid compound represented by the general formula (1) produced by the deprotection reaction for the carboxyl group in Step 3 is washed with water, filtered, concentrated, distilled, and It can be purified by a separation / purification method such as extraction or a combination thereof.
A preferred purification method is that after the deprotection reaction, an organic solvent and an alkaline aqueous solution are added to the reaction system, the (meth) acryloyloxyadamantanecarboxylic acid compound represented by the general formula (1) is neutralized, and extracted into an aqueous layer. In this method, an acidic compound is added to the recovered aqueous layer to neutralize the base in the aqueous solution, and the powder of the (meth) acryloyloxyadamantanecarboxylic acid compound is crystallized from the aqueous layer and recovered. High purity crystals can be obtained by this method.
In addition, after completion | finish of reaction, before the (meth) acryloyl oxyadamantane carboxylic acid compound represented by General formula (1) precipitates from an aqueous layer and collects, it is common by washing, filtration, concentration, extraction, etc. Separation and purification operations can be optionally performed.

  Organic solvents to be added are diethyl ether, diisopropyl ether, methyl t-butyl ether, cyclopentyl methyl ether, tetrahydrofuran, dioxane, hexane, heptane, octane, benzene, toluene, xylene, methicylene, pseudocumene, chloroform, chlorobenzene, 1,2- Examples thereof include dichloroethane, dichloromethane, methyl isobutyl ketone, and ethyl acetate. Preferably, hexane, heptane, octane, benzene, toluene, xylene, methicylene, pseudocumene, chloroform, chlorobenzene, 1,2- Dichloroethane, dichloromethane and the like are preferable, and hexane, heptane, octane, hexanebenzene, toluene, xylene, methicylene, and Hydrocarbon solvents such as pseudocumene is preferred. If these solvents are used, the affinity between the neutralized (meth) acryloyloxyadamantanecarboxylic acid compound and the solvent is low, and the (meth) acryloyloxyadamantanecarboxylic acid compound can be effectively recovered on the water layer side. it can.

  The amount of the organic solvent to be added is 1.0 to 100 times by mass, preferably 2.0 to 50 times by mass, more preferably 3.0 to 15 times by mass with respect to the hydroxyadamantanecarboxylic acid compound used as a raw material. is there.

  The alkali used in the alkaline aqueous solution to be added is sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, sodium dihydrogen phosphate, disodium phosphate, trisodium phosphate, potassium dihydrogen phosphate, phosphorus Tetraalkylammonium hydroxide such as dipotassium acid, tripotassium phosphate, ammonium hydroxide, tetramethylammonium hydroxide, and the like, especially sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, Inorganic bases such as sodium dihydrogen phosphate, disodium phosphate, trisodium phosphate, potassium dihydrogen phosphate, dipotassium phosphate, tripotassium phosphate, ammonium hydroxide, sodium hydroxide, and potassium hydroxide are inexpensive. Take Since treatment is easy preferable. Although the density | concentration of alkaline aqueous solution does not receive a restriction | limiting in particular, 1-30 mass% is preferable when general handling is considered, and the density | concentration of 10-20 mass% is more preferable. In addition, the amount of alkali added is 0.5 to 10 mol times the number of dissociable protons of the acidic compound used in the deprotection reaction, and the (meth) acryloyloxyadamantanecarboxylic acid compound is used in the middle. Use an amount that brings the pH of the aqueous layer that has been summed and recovered to 6.5 or higher.

  Acidic compounds added to the aqueous layer from which the (meth) acryloyloxyadamantanecarboxylic acid compound is recovered include inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid and phosphoric acid, formic acid, acetic acid, propionic acid, trifluoroacetic acid, methanesulfonic acid, Organic acids such as ethane sulfonic acid, propane sulfonic acid, trifluoromethyl sulfonic acid, and paratoluene sulfonic acid may be mentioned. These can be used individually by 1 type or in mixture of 2 or more types.

  The amount of the acidic compound added to the aqueous layer is 0.5 to 10 moles, preferably 1.0 to the alkaline compound used when the (meth) acryloyloxyadamantanecarboxylic acid compound is recovered in the aqueous layer. 3 mol times is used, and the amount that the pH of the aqueous layer is 7 or less is used.

  There is no particular limitation on the method for filtering the precipitated (meth) acryloyloxyadamantanecarboxylic acid compound, and a known method such as natural filtration using gravity, pressure filtration, vacuum filtration, and centrifugal separation can be selected. The shape can also be selected as desired, such as processes and equipment.

  The (meth) acryloyloxyadamantanecarboxylic acid compound separated by the filtration can be dried and handled as a powder. The drying method is not particularly limited, and can be selected from methods such as air drying, heat drying, and reduced pressure drying. However, reduced pressure drying that can shorten the drying time is preferably selected. Moreover, there is no restriction | limiting in particular in drying temperature, 0-120 degreeC is preferable if it is under normal pressure-pressure reduction, and 30-80 degreeC is more preferable.

  Next, a more preferable purification step of the (meth) acryloyloxyadamantanecarboxylic acid compound will be described.

  In the present invention, the recovered (meth) acryloyloxyadamantanecarboxylic acid compound is dissolved in an organic solvent having a specific composition, and activated carbon is added to remove byproducts such as a high molecular weight component having a molecular weight larger than the target product, It is possible to obtain a (meth) acryloyloxyadamantanecarboxylic acid compound of higher purity by distilling off the solvent of the solution and adding a solvent having low solubility of the (meth) acryloyloxyadamantanecarboxylic acid compound and recrystallization. it can.

  The (meth) acryloyloxyadamantane carboxylic acid compound used in the purification step is a powdery (meth) acryloyloxyadamantane carboxylic acid compound obtained by recrystallization after the step 3, or the acidic compound is added. When the powder is precipitated, an organic solvent may be added and extracted into the organic solvent for use. At that time, the organic solvent to be added is an organic solvent having a specific composition used in the purification step.

In the purification step of the (meth) acryloyloxyadamantanecarboxylic acid compound, an organic solvent having a specific composition is used by mixing two kinds of solvents.
As one of the solvents to be used, a solvent in which the (meth) acryloyloxyadamantanecarboxylic acid compound has high solubility is used. As the solvent, diethyl ether, diisopropyl ether, methyl-t-butyl ether, cyclopentyl methyl ether, tetrahydrofuran, dioxane, benzene, toluene, xylene, methicylene, pseudocumene, chloroform, chlorobenzene, 1,2-dichloroethane, dichloromethane, methyl isobutyl ketone, and Ethyl acetate and the like can be mentioned, but aromatic hydrocarbon solvents such as benzene, toluene, xylene, methicylene and pseudocumene, which have low solubility of the (meth) acryloyloxyadamantanecarboxylic acid compound, are preferable, and since toluene is inexpensive and easy to handle, It can be preferably used. The amount of the organic solvent to be used is preferably 1.0 to 20 times by mass with respect to the (meth) acryloyloxyadamantanecarboxylic acid compound from the viewpoint of sufficiently dissolving the (meth) acryloyloxyadamantanecarboxylic acid compound, and particularly 2. 0-10 mass times is more preferable.

  As the second solvent of the organic solvent having a specific composition, a solvent having low solubility of the (meth) acryloyloxyadamantanecarboxylic acid compound is used. Examples of the solvent include aliphatic hydrocarbon solvents such as heptane, hexane, heptane, and octane. However, hexane and heptane are preferable because they are inexpensive and easy to handle. The amount of the organic solvent to be used is preferably 1.0 to 20 times by mass, particularly 2.0 to 10 times by mass with respect to the amount of the solvent having high solubility of the (meth) acryloyloxyadamantanecarboxylic acid compound. preferable. By using two types of solvents as the organic solvent having the specific composition, it is possible to deposit and remove impurities while adsorbing to the activated carbon while sufficiently dissolving the (meth) acryloyloxyadamantanecarboxylic acid compound. Become.

There is no restriction | limiting in particular in the activated carbon used in the said refinement | purification process, You may use a commercial item. Examples of commercially available products include Nippon Enviro Chemicals Co., Ltd., Carlabafine, Kuraray Chemical Co., Ltd., and Kuraray Coal.
The amount of the activated carbon used is 0.0001 to 1 times by mass, preferably 0.001 to 0.5 times by mass, with respect to 100 parts by mass of the theoretical yield of the (meth) acrylolyloxyadamantanecarboxylic acid compound.
As specific reaction temperature and reaction time after addition of activated carbon, reaction temperature is generally 0 ° C to 100 ° C, preferably 10 ° C to 75 ° C, reaction time is 0.1 hour to 20 hours, preferably 1 hour to 10 hours. Time and pressure can be performed under normal pressure, reduced pressure or increased pressure. In addition, the reaction can be performed by appropriately selecting a known method such as a batch system, a semi-batch system, or a continuous system.

  There is no restriction | limiting in particular in the removal method of the activated carbon after the said use, Well-known methods, such as natural filtration using gravity, pressure filtration, reduced pressure filtration, and centrifugation, can be selected. Moreover, the shape of the filter used for filtration can also be selected as desired, such as process and equipment.

  When the solvent is distilled off in the purification step, the solvent is distilled off until the solution mass is 0.5 to 5.0 times the mass of the (meth) acryloyloxyadamantanecarboxylic acid compound. For example, an evaporator or the like can be used.

  The solvent having a low solubility of the (meth) acryloyloxyadamantanecarboxylic acid compound added after the solvent is distilled off is the same as that mentioned as the solvent having a low solubility. The usage-amount of a solvent is 0.5-5.0 times the mass of the whole solution after solvent distillation. Within this range, the amount of the (meth) acryloyloxyadamantanecarboxylic acid compound dissolved in the solvent is small, and the (meth) acryloyloxyadamantanecarboxylic acid compound can be obtained with a high yield.

  The method for separating the precipitated (meth) acryloyloxyadamantanecarboxylic acid compound is not particularly limited, and known methods such as natural filtration using gravity, pressure filtration, filtration under reduced pressure, and centrifugation can be selected. The shape of the filter used for filtration can also be selected as desired, such as process and equipment.

  The (meth) acryloyloxyadamantanecarboxylic acid compound separated by the filtration can be dried and handled as a powder. The drying method is not particularly limited, and can be selected from methods such as air drying, heat drying, and reduced pressure drying. However, reduced pressure drying that can shorten the drying time is preferably selected. Moreover, there is no restriction | limiting in particular in drying temperature, 0-120 degreeC is preferable if it is under normal pressure-pressure reduction, and 30-80 degreeC is more preferable.

EXAMPLES Hereinafter, although an Example demonstrates this invention concretely, this invention does not receive a restriction | limiting at all to a following example. In the examples, the change with time and the yield were measured by gas chromatography (GC) or high performance liquid chromatography (HPLC).
The purity of the hydroxyadamantanecarboxylic acid compound was determined by GC and gel permeation chromatography (GPC), and the purity of the derivative methacryloyloxyadamantanecarboxylic acid compound was determined by HPLC and GPC. The measurement conditions for GC, HPLC, and GPC are as follows. In addition, unless otherwise indicated, the part and% in an example are each mass part and mass%.

<GC conditions>
Column: TC-17 (0.53 mm ID × 30 m), injection temperature: 280 ° C., oven temperature: 70 ° C. (1 minute hold) → temperature rise at 10 ° C./minute→280° C. (10 minute hold), detection Vessel: FID, mobile phase: helium

<HPLC measurement conditions>
Column: Chemical substance evaluation mechanism L-column 2 ODS L-C18 (5 μm, 4.6 φ × 250 mm), developing solvent: acetonitrile / 100 mM phosphate buffer = 70/30 (v / v), flow rate: 1 mL / min, column Temperature: 40 ° C, Detector: RI

<GPC conditions>
Showa Denko GPC columns (2 K401HQ, 1 KF402HQ, 1 KF403HQ, KF-G), flow rate: 1.0 ml / min, elution solvent: tetrahydrofuran,
Column temperature: The abundance was measured as standard polystyrene equivalent mass under the analysis conditions of 40 ° C.

Example 1
(Step 1) A glass 500 mL flask equipped with a stirrer, a thermometer, a dropping funnel, and a Dim funnel as a reaction apparatus was charged with 19.6 g (100 mmol) of 3-hydroxyadamantane-1-carboxylic acid, and the reaction vessel was purged with nitrogen. After adding 29.4 g of methoxycyclopentane and 30.3 g (300 mmol) of triethylamine to the reaction vessel, the reaction vessel was stirred in an ice bath at a temperature of 10 ° C. or lower. To the dropping funnel, 8.4 g (105 mmol) of chloromethyl methyl ether was added and added dropwise over 15 minutes. After completion of the dropping, the reaction was carried out at a reaction solution temperature of 10 ° C. for 1 hour.
When the progress of the reaction was confirmed by GC, the conversion rate of 3-hydroxyadamanta-1-carboxylic acid was 93%, and methoxymethyl-3-hydroxyadamantane-1-carboxylate was found to have a reaction yield of 85.0%. Generated. (Step 2) Thereafter, 98 g of chloroform and 0.2 g (1 mmol) of phenothiazine were added while the flask was bathed in ice. A dropping funnel was charged with 15.7 g (150 mmol) of methacrylic acid chloride and added dropwise over 15 minutes with an ice bath. After completion of dropping, the reaction was carried out at a reaction solution temperature of 70 ° C. for 10 hours.
When the progress of the reaction was confirmed by GC, the conversion of methoxymethyl-3-hydroxyadamantane-1-carboxylate was 98%, and the reaction yield based on the charged amount of 3-hydroxyadamantane-1-carboxylic acid 82% produced methoxymethyl-3- (methacryloyloxy) adamantane-1-carboxylate. After cooling the reaction vessel to 20 ° C. or lower with an ice bath, 100 g of chloroform and 200 g of ion-exchanged water were added, stirred for 5 minutes, and allowed to stand for 5 minutes, followed by liquid separation operation.
200 g of 5% aqueous sodium hydrogen carbonate solution was added to the resulting chloroform layer, stirred for 5 minutes, and allowed to stand for 5 minutes, followed by liquid separation operation. As a washing operation of the obtained chloroform layer, 100 g of ion exchange water was added and stirred for 5 minutes, and then allowed to stand for 5 minutes, and then a liquid separation operation was performed. This washing operation was performed twice in total. The solvent of the collected chloroform layer was distilled off using an evaporator. The resulting concentrate was used in the next step without further purification.

(Step 3) The obtained concentrate, 31.0 g of tetrahydrofuran and 30 g of 1.0 mol / L hydrochloric acid were added to a 1 L glass flask equipped with a stirrer, a thermometer, a dropping funnel and a Dim funnel. The reaction solution was stirred at a temperature of 60 to 70 ° C. for 6 hours.
When the progress of the reaction was confirmed by HPLC, the conversion rate of methoxymethyl-3- (methacryloyloxy) adamantane-1-carboxylate was 100%, and based on the charged amount of 3-hydroxyadamantane-1-carboxylic acid, 3-Methacryloyloxyadamantane-1-carboxylic acid was produced with a reaction yield of 80%. The reaction vessel was cooled to 20 ° C. or lower with an ice bath, 550 g of 5% aqueous sodium hydrogen carbonate solution and 120 g of heptane were added, and the mixture was stirred for 1 hour. After completion of stirring, the mixture was allowed to stand for 5 minutes, and then a liquid separation operation was performed. After the separation, 150 g of 5% aqueous sodium hydrogen carbonate solution was added to the organic layer, and the mixture was stirred for 5 minutes.
While stirring the obtained aqueous layer, 65 g of 85% phosphoric acid was added to precipitate a powdery solid of 3-methacryloyloxyadamantane-1-carboxylic acid from the aqueous layer. The precipitated solid was recovered by suction filtration and washed twice with 50 g of ion exchange water. The solid was dried under reduced pressure to obtain 19.0 g of 3-methacryloyloxyadamantane-1-carboxylic acid. The yield was 72% based on the amount of 3-hydroxyadamantane-1-carboxylic acid charged. The purity of 3-methacryloyloxyadamantane-1-carboxylic acid was HPLC-RI 99.0%, and the abundance of high molecular weight components was GPC-RI 6.8% and GPC-RI 0.7%.

(Example 2)
The same operation as in Example 1 was performed except that acrylic acid chloride was used instead of methacrylic acid chloride. 17.5 g of a powdery 3-acryloyloxyadamantane-1-carboxylic acid solid was obtained. The yield was 70% based on the charged amount of 3-hydroxyadamantane-1-carboxylic acid. The purity of 3-acryloyloxyadamantane-1-carboxylic acid was HPLC-RI 99.1%, and the abundance of high molecular weight components was GPC-RI 10.8% and GPC-RI 1.5%.

(Example 3)
(Step 1) A glass 500 mL flask equipped with a stirrer, a thermometer, a dropping funnel, and a Dim funnel as a reaction apparatus was charged with 19.6 g (100 mmol) of 3-hydroxyadamantane-1-carboxylic acid, and the reaction vessel was purged with nitrogen. After adding 29.4 g of methoxycyclopentane and 30.3 g (300 mmol) of triethylamine to the reaction vessel, the reaction vessel was stirred in an ice bath at a temperature of 10 ° C. or lower. To the dropping funnel, 8.4 g (105 mmol) of chloromethyl methyl ether was added and added dropwise over 15 minutes. After completion of the dropping, the reaction was carried out at a reaction solution temperature of 0 to 20 ° C. for 1 hour.
When the progress of the reaction was confirmed by GC, the conversion rate of 3-hydroxyadamanta-1-carboxylic acid was 93%, and methoxymethyl-3-hydroxyadamantane-1-carboxylate was found to have a reaction yield of 85.0%. Generated. (Step 2) Thereafter, 98 g of chloroform and 0.2 g (1 mmol) of phenothiazine were added while the flask was bathed in ice. A dropping funnel was charged with 15.7 g (150 mmol) of methacrylic acid chloride and added dropwise over 15 minutes with an ice bath. After completion of dropping, the reaction was carried out at a reaction solution temperature of 70 ° C. for 10 hours.
When the progress of the reaction was confirmed by GC, the conversion of methoxymethyl-3-hydroxyadamantane-1-carboxylate was 98%, and the reaction yield based on the charged amount of 3-hydroxyadamantane-1-carboxylic acid 82% produced methoxymethyl-3- (methacryloyloxy) adamantane-1-carboxylate. After cooling the reaction vessel to 20 ° C. or lower with an ice bath, 100 g of chloroform and 200 g of ion-exchanged water were added, stirred for 5 minutes, and allowed to stand for 5 minutes, followed by liquid separation operation. 200 g of 5% aqueous sodium hydrogen carbonate solution was added to the resulting chloroform layer, stirred for 5 minutes, and allowed to stand for 5 minutes, followed by liquid separation operation. As a washing operation of the obtained chloroform layer, 100 g of ion exchange water was added and stirred for 5 minutes, and then allowed to stand for 5 minutes, and then a liquid separation operation was performed. This washing operation was performed twice in total. The solvent of the collected chloroform layer was distilled off using an evaporator. The resulting concentrate was used in the next step without further purification.

(Step 3) The obtained concentrate, 31.0 g of tetrahydrofuran, and 30 g of 1.0 mol / L hydrochloric acid were added to a glass 1 L flask equipped with a stirrer, a thermometer, a dropping funnel, and a Dim funnel. The reaction solution was stirred at a temperature of 60 to 70 ° C. for 6 hours. When the progress of the reaction was confirmed by HPLC, the conversion rate of methoxymethyl-3- (methacryloyloxy) adamantane-1-carboxylate was 100%, and based on the charged amount of 3-hydroxyadamantane-1-carboxylic acid, 3-Methacryloyloxyadamantane-1-carboxylic acid was produced with a reaction yield of 80%. The reaction vessel was cooled to 20 ° C. or lower with an ice bath, 550 g of 5% aqueous sodium hydrogen carbonate solution and 120 g of heptane were added, and the mixture was stirred for 1 hour. After completion of stirring, the mixture was allowed to stand for 5 minutes, and then a liquid separation operation was performed. After the separation, 150 g of 5% aqueous sodium hydrogen carbonate solution was added to the organic layer, and the mixture was stirred for 5 minutes.
To the obtained aqueous layer, 10 g of toluene and 30 g of heptane were added, and then 100 g of 85% phosphoric acid was added with stirring to extract 3-methacryloyloxyadamantane-1-carboxylic acid into the organic layer, and a liquid separation operation was performed. . After the liquid separation operation was further performed twice using 200 g of ion-exchanged water for the organic layer, 2.0 g of activated carbon (Carboraphin, Nippon Environmental Chemicals) was added and stirred at 40 ° C. for 1 hour. Components insoluble in the solvent and activated carbon were removed by suction filtration, and the filtrate was washed with a mixed solution of 20 g of toluene and 60 g of heptane. The filtrate was collected and the solvent was distilled off under reduced pressure until the solution mass reached 40 g. Thereafter, 100 g of heptane was added, and the mixture was stirred for 1 hour in an ice bath to precipitate white crystals of 3-methacryloyloxyadamantane-1-carboxylic acid. The precipitated crystals were suction filtered and dried under reduced pressure to obtain 17.0 g of 3-methacryloyloxyadamantane-1-carboxylic acid. The yield was 64% based on the charged amount of 3-hydroxyadamantane-1-carboxylic acid. The purity of 3-methacryloyloxyadamantane-1-carboxylic acid was 99.9% by HPLC-RI, and the abundance of high molecular weight components was 0.3% by GPC-RI and 0.2% by GPC-RI.

Example 4
<Purification operation 1>
To 19.0 g of 3-methacryloyloxyadamantane-1-carboxylic acid obtained in Example 1 were added 57 g of toluene, 171 g of heptane, and 1.2 g of activated carbon (Carboraphin, Nippon Environmental Chemicals), and the mixture was stirred at 40 ° C. for 1 hour. After removing components insoluble in the solvent and activated carbon by suction filtration, the solvent was distilled off under reduced pressure using an evaporator until the mass of the solution reached 36 g. Thereafter, 95 g of heptane was added, and the mixture was stirred for 1 hour in an ice bath to precipitate white crystals of 3-methacryloyloxyadamantane-1-carboxylic acid. The precipitated crystals were suction filtered and dried under reduced pressure to obtain 17.2 g of 3-methacryloyloxyadamantane-1-carboxylic acid. The crystal recovery rate in the purification operation was 90.5%, and the overall yield through Example 1 and Example 4 was 65% based on the charged amount of 3-hydroxyadamantane-1-carboxylic acid. The purity of 3-methacryloyloxyadamantane-1-carboxylic acid was 99.9% by HPLC-RI, and the abundance of high molecular weight components was 0.3% by GPC-RI and 0.2% by GPC-RI.

(Example 5)
<Purification operation 2>
The same operation as in Example 4 was carried out except that 3-acryloyloxyadamantane-1-carboxylic acid obtained in Example 2 was used. As a result, 16.3 g of 3-acryloyloxyadamantane-1-carboxylic acid was obtained. The crystal recovery rate in the purification operation was 90.5%, and the overall yield through Example 2 and Example 5 was 65% based on the charged amount of 3-hydroxyadamantane-1-carboxylic acid. . The purity was 99.9% by HPLC-RI, and the abundance of high molecular weight components was 0.3% by GPC-RI and 0.3% by GPC-RI.

(Comparative Example 1)
19.6 g (100 mmol) of 3-hydroxyadamantane-1-carboxylic acid and 0.2 g (1 mmol) of phenothiazine were charged in a 1 L glass flask equipped with a stirrer, thermometer, dropping funnel and Dim funnel as a reaction apparatus. Replaced with nitrogen. To the reaction vessel, 98 g of dichloroethane and 30.3 g (300 mmol) of triethylamine were added, followed by ice bathing, and the reaction solution temperature was stirred at 10 ° C. or lower. A dropping funnel was charged with 31.4 g (300 mmol) of methacrylic acid chloride and added dropwise over 15 minutes with an ice bath. After completion of dropping, the reaction was carried out at a reaction solution temperature of 80 ° C. for 5 hours. When the progress of the reaction was confirmed by HPLC, the conversion of 3-hydroxyadamantane-1-carboxylic acid was 100%, and 3-methacryloyloxyadamantane-1-carboxylic acid was produced at a reaction yield of 58.8%. After cooling the reaction vessel to 20 ° C. or less with an ice bath, 50 g of toluene and 400 g of 5% aqueous sodium hydroxide solution were added and stirred for 1 hour. After completion of stirring, the mixture was allowed to stand for 5 minutes, and then a liquid separation operation was performed. After the separation, 100 g of 5% aqueous sodium hydroxide solution was added to the organic layer, and after stirring well, the mixture was allowed to stand for 5 minutes, followed by a liquid separation operation. While stirring the obtained aqueous layer, 65 g of 85% phosphoric acid was added thereto, and a clay-like mixture containing 3-methacryloyloxyadamantane-1-carboxylic acid was precipitated. The clay-like mixture was filtered off to obtain 20 g of a solid containing 3-methacryloyloxyadamantane-1-carboxylic acid. The purity of 3-methacryloyloxyadamantane-1-carboxylic acid in the solid was 70% by HPLC-RI.

(Comparative Example 2)
In a 500 mL glass flask equipped with a stirrer, thermometer, Dean-Stark tube and Dimroth as a reaction apparatus, 19.6 g (100 mmol) of 3-hydroxyadamantane-1-carboxylic acid, 98 g of toluene, 25.8 g (300 mmol) of methacrylic acid Then, 0.98 g (10 mmol) of sulfuric acid and 62 mg (0.5 mmol) of p-methoxyphenol were charged, and the reaction solution was heated to reflux at 110 ° C. for 4 hours.
When the progress of the reaction was confirmed by GC, the conversion of 3-hydroxyadamantane-1-carboxylic acid was 98%, and 3- (methacryloyloxy) adamantane-1-carboxylic acid was produced at a reaction yield of 52%. After cooling the reaction vessel to 20 ° C. or lower with an ice bath, 50 g of toluene and 400 g of 5% aqueous sodium hydroxide solution were added and stirred for 1 hour. After completion of stirring, the mixture was allowed to stand for 5 minutes, and then a liquid separation operation was performed. After the separation, 100 g of 5% aqueous sodium hydroxide solution was added to the organic layer, and the mixture was stirred for 5 minutes. While stirring the obtained aqueous layer, 65 g of 85% phosphoric acid was added thereto, and a clay-like mixture containing 3-methacryloyloxyadamantane-1-carboxylic acid was precipitated. The clay-like mixture was separated by filtration to obtain 22 g of solid containing 3-methacryloyloxyadamantane-1-carboxylic acid. The purity of 3-methacryloyloxyadamantane-1-carboxylic acid in the solid was 60% by HPLC-RI.

(Comparative Example 3)
<Purification operation 3>
When the same operation as in Example 3 was performed without using activated carbon (Carborafine, Nippon Envirochemicals), a highly viscous solid was obtained, and the abundance of the high molecular weight component was not changed.

Claims (11)

A method for producing a compound represented by formula (1) as a high-purity compound having the following steps :
Step 1: a step of reacting a compound represented by formula (2) with a halogenated methyl alkyl ether represented by formula (3) to protect a carboxyl group to obtain a compound represented by formula (4) ;
Step 2: A step of adding (meth) acrylic acid chloride to the reaction solution of Step 1 to convert the hydroxyl group to (meth) acrylic ester to obtain a compound represented by the formula (5);
Process 3: The process made into the compound represented by Formula (1) by deprotecting the protective group of the carboxyl group which the compound represented by Formula (5) has;
Step 4: The compound represented by the formula (1) obtained in Step 3 is washed with an alkali, neutralized and extracted as a salt in an aqueous layer, and then an acidic compound is added to perform crystallization separation. The process to perform.
(In the formula, R ¹ is bonded to carbons other than the bridge head position, each independently represents hydrogen or an alkyl group having 1 to 6 carbon atoms, and m = 12. R ² represents n COOH, p And q alkyl groups having 1 to 6 carbon atoms, n, p and q are natural numbers having a relationship of n = 1 to 3 and n + p + q = 3, and R ³ represents a hydrogen or methyl group. Show.)

(In the formula, R ¹ and R ² have the same meanings as in formula (1).)

(In the formula, X is a halogen, and the substituent R ⁴ represents an alkyl group having 1 to 12 carbon atoms.)

(In the formula, R ⁵ represents n COOCH ₂ OR ⁴ , p hydrogen and q alkyl groups having 1 to 6 carbon atoms. R ¹ , m, n, p and q are represented by the formula (2). And R ⁴ is synonymous with formula (3).
(In the formula, R ¹ and R ³ have the same meaning as in formula (1), and R ⁵ has the same meaning as in formula (4).) The method to manufacture the compound represented by Formula (1) of Claim 1 as a high purity compound whose X in the said Formula (3) is chlorine. The method to manufacture the compound represented by Formula (1) of Claim 2 as a high purity compound whose said halogenated methyl alkyl ether is chloromethyl methyl ether. The method of manufacturing the compound represented by Formula (1) as described in any one of Claims 1-3 as a high purity compound which performs reaction of the said process 2 in a halogen solvent. In the formula (1) according to any one of claims 1 to 4, wherein the deprotection reaction in the step 3 is a reaction of water and a compound represented by the formula (5) in the presence of an acidic catalyst. A method for producing the represented compound as a high-purity compound . The method to manufacture the compound represented by Formula (1) as described in any one of Claims 1-5 as a high purity compound whose alkali used for the said alkali washing is sodium hydrogencarbonate. The said acidic compound is phosphoric acid, The method to manufacture the compound represented by Formula (1) as described in any one of Claims 1-6 as a high purity compound . After adding the acidic compound, further obtained by adding a solvent and activated carbon to remove by-products, then distilling off the solvent of the solution and further adding a poor solvent for crystallization separation. The method to manufacture the compound represented by Formula (1) as described in any one of 1-7 as a high purity compound . After adding a solvent and activated carbon to the compound represented by the formula (1) obtained by the crystallization separation performed after the alkali washing to remove by-products, the solvent of the solution is distilled off, and a poor solvent is further added. The method of manufacturing the compound represented by Formula (1) as described in any one of Claims 1-7 obtained by performing crystallization separation as a high purity compound . The method to manufacture the compound represented by Formula (1) of Claim 8 or 9 as a high purity compound that the solvent added with the said activated carbon contains an aliphatic hydrocarbon solvent. High molecular weight component containing as impurities, GPC-UV1.0% or less, or less GPC-RI1.0%, the compound represented by the formula (1) according to any one of claims 8-10 A method for producing as a high purity compound .