JPS6025425B2 - Synthesis method of substituted phenoxy fatty acids - Google Patents
Synthesis method of substituted phenoxy fatty acidsInfo
- Publication number
- JPS6025425B2 JPS6025425B2 JP2786975A JP2786975A JPS6025425B2 JP S6025425 B2 JPS6025425 B2 JP S6025425B2 JP 2786975 A JP2786975 A JP 2786975A JP 2786975 A JP2786975 A JP 2786975A JP S6025425 B2 JPS6025425 B2 JP S6025425B2
- Authority
- JP
- Japan
- Prior art keywords
- salts
- formula
- substituted phenoxy
- fatty acids
- salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- -1 phenoxy fatty acids Chemical class 0.000 title claims description 12
- 235000014113 dietary fatty acids Nutrition 0.000 title claims description 9
- 239000000194 fatty acid Substances 0.000 title claims description 9
- 229930195729 fatty acid Natural products 0.000 title claims description 9
- 238000001308 synthesis method Methods 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
- 125000004494 ethyl ester group Chemical group 0.000 description 5
- 239000002585 base Substances 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 150000004665 fatty acids Chemical class 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical class CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229940090012 bentyl Drugs 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- GUBNMFJOJGDCEL-UHFFFAOYSA-N dicyclomine hydrochloride Chemical group [Cl-].C1CCCCC1C1(C(=O)OCC[NH+](CC)CC)CCCCC1 GUBNMFJOJGDCEL-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 159000000003 magnesium salts Chemical class 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 159000000001 potassium salts Chemical class 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000012264 purified product Substances 0.000 description 2
- 150000003222 pyridines Chemical class 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 235000010005 Catalpa ovata Nutrition 0.000 description 1
- 240000004528 Catalpa ovata Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 235000010650 Hyssopus officinalis Nutrition 0.000 description 1
- 240000001812 Hyssopus officinalis Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 229940053200 antiepileptics fatty acid derivative Drugs 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical class C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- OMRRUNXAWXNVFW-UHFFFAOYSA-N fluoridochlorine Chemical compound ClF OMRRUNXAWXNVFW-UHFFFAOYSA-N 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Chemical group 0.000 description 1
Landscapes
- Thiazole And Isothizaole Compounds (AREA)
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【発明の詳細な説明】
この発明は新規な置換フェノキシ脂肪酸類の合成法に関
するものであり、その概略を式で示すと次の通りである
。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for synthesizing substituted phenoxy fatty acids, and the outline thereof is shown by the following formula.
またはその塩類
またはその塩類
（式中、Ｒ，およびＲ２は水素またはアルキル基、Ｒ３
はアルキル基でェステル化されたカルボキシ基、Ｒ４は
ペンゾチアゾリルまたはビリジル、Ｙは酸残基、Ａはア
ルキレン基をそれぞれ意味する）この発明で原料物質と
して使用する脂肪酸誘導体（１）およびその塩類は新規
化合物であり、そのうち例えば、２−（４−プロモメチ
ルフェノキシ）一２−メチルプロピオン酸のエチルェス
テルは２一（Ｐートリルオキシ）−２−メチルプロピオ
ン酸のエチルェステルにＮ−ブロモサクシンィミドを作
用させるこ，とにより製造することができる。or a salt thereof or a salt thereof (wherein R and R2 are hydrogen or an alkyl group, R3
is a carboxy group esterified with an alkyl group, R4 is penzothiazolyl or biridyl, Y is an acid residue, and A is an alkylene group.) The fatty acid derivative (1) and its salts used as raw materials in this invention are novel. For example, the ethyl ester of 2-(4-promomethylphenoxy)-2-methylpropionic acid can be obtained by treating the ethyl ester of 2-(P-tolyloxy)-2-methylpropionic acid with N-bromosuccinimide. , and can be manufactured by.
この発明の反応は脂肪酸誘導体（１）またはその塩類に
アミン酸（ロ）を作用させることにより行なわれる。The reaction of this invention is carried out by reacting the fatty acid derivative (1) or its salt with an amino acid (b).
脂肪酸誘導体とは前記一般式（１）で示され、さらに詳
細には同一もしくは異つて水素またはメチル、エチル、
プロピル、イソプ。The fatty acid derivative is represented by the above general formula (1), and more specifically, the same or different hydrogen, methyl, ethyl,
Propyl, Isop.
ピル、ブチル、ィソブチル、第３級ブチル、ベンチル、
ヘキシル等のアルキル基をＲ，およびＲ２として有し、
アルキル基でェステル化されたカルボキシ基をＲ３とし
て有し、クロル、フルオル、フロム等のハロゲン、ベン
ゼンスルホニルオキシ、トシルオキシ、４−プロモベン
ゼンスルホニルオキシ、４ークロロベンゼンスルホニル
オキシ、メシルオキシ、ェタンスルホニルオキシ等のア
レーンもしくはアルカンスルホニルオキシ基等の酸残基
をＹとして有し、メチレン、エチレン、メチルエチレン
、プロピレンｈトリメチレン、２ーメチルトリメチレン
等のアルキレン基をＡとして有する化合物を意味する。
ここにおいてＲ３のアルキル基でェステル化されたカル
ボキシ基としては、例えば、そのェステル部分がメチル
、エチル、プロピル、ィソプロピル、ブチル、第３級ブ
チル、ベンチル、シクロヘキシル、シクｏヘプチル、ビ
ニル、１−プロベニル、アリル、１・１−ジメチル−２
−プロベニル、３−ブテニル、１・１−ジメチル−２ー
プロピニル等の飽和もしくは不飽和、鎖状もしくは環状
のアルキルであるヱステルが挙げられる。また脂肪酸議
導体（１）の塩類としては、ナトリウム塩、カリウム塩
、カルシウム塩、マグネシウム塩等の無機塩基との塩、
トリメチルァミン塩、トリヱチルアミン塩、Ｎ・Ｎージ
メチルアニリン塩、ピリジン塩、ピコリン塩、Ｎ・Ｎ′
−ジベンジルェチレンジアミン塩等の有機塩基との塩が
挙げられる。アミン類とは前記一般式（０）で示され、
さらに詳細には、ベンゾチアゾリルまたはビリジルをＲ
４として有する化合物を意味する。pill, butyl, isobutyl, tertiary butyl, bentyl,
Having an alkyl group such as hexyl as R and R2,
It has a carboxy group esterified with an alkyl group as R3, and includes halogens such as chlor, fluor, and flom, benzenesulfonyloxy, tosyloxy, 4-promobenzenesulfonyloxy, 4-chlorobenzenesulfonyloxy, mesyloxy, ethanesulfonyloxy, etc. It means a compound having as Y an acid residue such as an arene or alkanesulfonyloxy group, and having as A an alkylene group such as methylene, ethylene, methylethylene, propylene htrimethylene, or 2-methyltrimethylene.
Here, examples of the carboxy group esterified with an alkyl group of R3 include, for example, the ester portion thereof is methyl, ethyl, propyl, isopropyl, butyl, tertiary butyl, bentyl, cyclohexyl, cycloheptyl, vinyl, 1-probenyl. , allyl, 1,1-dimethyl-2
Examples include esters which are saturated or unsaturated, chain or cyclic alkyls such as -probenyl, 3-butenyl and 1,1-dimethyl-2-propynyl. Salts of the fatty acid derivative (1) include salts with inorganic bases such as sodium salts, potassium salts, calcium salts, and magnesium salts;
Trimethylamine salt, triethylamine salt, N・N-dimethylaniline salt, pyridine salt, picoline salt, N・N′
-Salts with organic bases such as dibenzylethylenediamine salts are mentioned. Amines are represented by the above general formula (0),
More specifically, benzothiazolyl or biridyl is R
It means a compound having as 4.
この反応は通常溶媒中で行なわれ、溶媒としては、水、
ェタ／−ル、アセトン、エーテル、ジメチルホルムアミ
ド等が挙げられるが、これらに限定されるものではなく
、この反応に悪影響を及ぼさない溶媒はすべて使用する
ことができる。This reaction is usually carried out in a solvent, such as water,
Examples include, but are not limited to, ethyl alcohol, acetone, ether, dimethylformamide, etc. Any solvent that does not adversely affect this reaction can be used.
反応温度は、特に限定されないが、通常、冷却下〜室温
で行なわれることが多い。この反応は、一般に水素化ナ
トリウム、水素化カリウム等の水素化アルカリ金属、水
酸化ナトリウム、水酸化カリウム等の水酸化アルカリ金
属、炭酸ナトリウム、炭酸カリウム等の炭酸アルカリ金
属、炭酸水素ナトリウム、炭酸水素カリウム等の炭酸水
素アルカリ金属、トリメチルアミン、トリェチルアミン
等のトリァルキルアシン等の塩基の存在下に行なえば進
行しやすい。Although the reaction temperature is not particularly limited, it is usually carried out under cooling to room temperature. This reaction generally involves alkali metal hydrides such as sodium hydride and potassium hydride, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, sodium hydrogen carbonate, and hydrogen carbonate. The reaction progresses easily if carried out in the presence of an alkali metal hydrogen carbonate such as potassium, or a base such as trialkylacine such as trimethylamine or triethylamine.
アミン類（ロ）が塩基を兼ねることもでき、塩基のうち
液体のものは、溶媒を兼ねて使用することができる。こ
うして得られる置換フェノキシ脂肪酸議導体（ｍ）およ
びその塩類はその塩酸塩、臭化水素酸塩、硫酸塩等の無
機酸との塩、酢酸塩、マレィン酸塩、フマール酸塩、酒
石酸塩、ベンゼンスルホン酸塩、トルェンスルホン酸塩
等の有機酸との塩等の酸塩またはナトリウム塩、カリウ
ム塩、カルシウム塩、マグネシウム塩等の無機塩基との
塩、トリェチルアミン塩、ピリジン塩、Ｎ・Ｎ−ジメチ
ルアニリン塩等の有機塩基との塩等の塩基との塩に導い
てもよい。The amines (b) can also serve as a base, and liquid bases can also be used as a solvent. The thus obtained substituted phenoxy fatty acid derivative (m) and its salts include its salts with inorganic acids such as hydrochloride, hydrobromide, sulfate, acetate, maleate, fumarate, tartrate, and benzene salts. Acid salts such as salts with organic acids such as sulfonates and toluenesulfonates; salts with inorganic bases such as sodium salts, potassium salts, calcium salts, and magnesium salts; triethylamine salts, pyridine salts, N/N- It may also be converted into a salt with a base such as a salt with an organic base such as dimethylaniline salt.
この発明の目的物質である贋換フェノキシ脂肪酸誘導体
（ｍ）およびその塩類は、新規物質であって、コレステ
ロール低下作用を有し、医薬として有用である。The target substances of this invention, the falsified phenoxy fatty acid derivatives (m) and their salts, are new substances, have a cholesterol-lowering effect, and are useful as medicines.
次にこの発明を実施例により説明する。Next, the present invention will be explained with reference to examples.
実施例 １
２ーベンゾチアゾールアミン４．班夕をジメチルホルム
アミド４９の‘に溶解し、この溶液に氷冷縄梓下５０％
水素化ナトリウム１．７６夕を少量ずつ加え同温度で１
．虫時間燈枠する。Example 1 2-Benzothiazolamine4. Dissolve Hanyu in 49% dimethylformamide and add 50% ice-cold rope Azusa to this solution.
Add 1.76 liters of sodium hydride little by little at the same temperature.
．． Insect time light frame.
次いでこの溶液に、２−（４−フロモメチルフエノキシ
）−２−メチルプロピオン酸のエチルェステル１０．０
夕をジメチルホルムアミド１０の‘に溶解した溶液を氷
袷鷹梓下に滴下し、同温度で１．５時間頚拝する。反応
液にメタノール３０の‘を加え、次いで水を加えたのち
エーテルで４回抽出する。抽出液を４回水洗後、硫酸マ
グネシウムで乾燥し、溶媒を留去すると、油分１０．８
４夕を得る。この油分をシリカゲル１００夕を用い、２
％メタノール・ベンゼンを展開溶媒としてカラムクロマ
トグラフィーに付して精製すると油分３．９２夕を得る
。この油分を塩酸・エタノール溶液を用いて常法により
塩酸塩に導くと、２−〔４−（２−ペンゾチアゾリルア
ミノメチル）フエノキシ〕−２−メチルブロピオン酸の
エチルェステルの塩酸塩２．０４夕を得る。ｍｐｌ９３
〜１９８００。この結晶をエタノール２４の‘から再結
晶し、これを炉取すると、ｍｐ２１９〜２２０ｑｏの精
製品１．３夕を得る。一方、炉液から溶媒を蟹去し、残
澄をエタノール５の上から再結晶し、活性炭で処理する
と、同じくｍｐ２１９〜２２０ｏｏの精製品０．２夕を
得る。実施例 ２２ーピリジンアミソ６．２５夕および
粉末炭酸カリウム９．１８夕をジメチルホルムアミド６
２の‘に懸濁した液に氷袷雛枠下、２−（４−フロモメ
チルフェノキシ）−２ーメチルプロピオン酸のエチルェ
ステル２０．０夕をジメチルホルムアミド２０叫に溶解
した溶液を３０分間で滴下し、同温度で２時間縄拝する
。This solution was then added with 10.0 ml of the ethyl ester of 2-(4-furomomethylphenoxy)-2-methylpropionic acid.
A solution of dimethylformamide dissolved in 10 parts of dimethylformamide was added dropwise to the ice cream, and the mixture was kept at the same temperature for 1.5 hours. To the reaction solution was added 30% methanol, then water was added, and the mixture was extracted four times with ether. The extract was washed with water four times, dried over magnesium sulfate, and the solvent was distilled off, resulting in an oil content of 10.8
Get 4 evenings. This oil was mixed with 100% silica gel for 2 hours.
The product was purified by column chromatography using % methanol/benzene as a developing solvent to obtain an oil content of 3.92%. When this oil is converted into a hydrochloride by a conventional method using a hydrochloric acid/ethanol solution, the hydrochloride of the ethyl ester of 2-[4-(2-penzothiazolyl aminomethyl)phenoxy]-2-methylpropionic acid 2 Get .04 evening. mpl93
~19800. The crystals are recrystallized from 24 ml of ethanol and taken in a furnace to obtain 1.3 qo of purified product with mp of 219 to 220 qo. On the other hand, when the solvent is removed from the furnace liquid and the residue is recrystallized from ethanol 5 and treated with activated carbon, a purified product of 0.2 liters having the same mp of 219 to 220 oo is obtained. Example 2 6.25% of 2-pyridine amino and 9.18% of powdered potassium carbonate were dissolved in dimethylformamide.
A solution of 20.0 mg of ethyl ester of 2-(4-furomomethylphenoxy)-2-methylpropionic acid dissolved in 20.0 mm of dimethylformamide was added to the solution suspended in 2-2 for 30 minutes. Drop it and keep it at the same temperature for 2 hours.
Claims (1)
Ｒ＿３はアルキル基でエステル化されたカルボキシ基、
Ｙは酸残基、Ａはアルキレン基をそれぞれ意味する）で
示される脂肪酸誘導体またはその塩類に一般式 Ｒ＿４
−ＮＨ＿２（式中、Ｒ＿４はベンゾチアゾリルまたはビ
リジルを意味する）で示されるアミン類を作用させて一
般式 ▲数式、化学式、表等があります▼ （式中、Ｒ＿１、Ｒ＿２、Ｒ＿３、Ｒ＿４およびＡは前
と同じ意味）で示される置換フエノキシ脂肪酸誘導体ま
たはその塩類を得ることを特徴とする置換フエノキシ脂
肪酸類の合成法。[Claims] 1 General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R_1 and R_2 are hydrogen or an alkyl group,
R_3 is a carboxy group esterified with an alkyl group,
(Y means an acid residue, A means an alkylene group) or its salts with the general formula R_4
-NH_2 (in the formula, R_4 means benzothiazolyl or biridyl) is reacted with an amine to form the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (in the formula, R_1, R_2, R_3, R_4 and A are A method for synthesizing substituted phenoxy fatty acids, characterized by obtaining a substituted phenoxy fatty acid derivative or a salt thereof represented by (same meaning as above).
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2786975A JPS6025425B2 (en) | 1975-03-06 | 1975-03-06 | Synthesis method of substituted phenoxy fatty acids |
| GB2210075A GB1503953A (en) | 1974-06-04 | 1975-05-22 | Substituted-phenyl substituted-alkyl ethers and the preparation thereof |
| DK248875A DK248875A (en) | 1974-06-04 | 1975-06-03 | PROCEDURE FOR MAKING SUBSTITUTED PHENYL SUBSTITUTED ALKYLETHERS |
| FR7517497A FR2273518A1 (en) | 1974-06-04 | 1975-06-04 | SUBSTITUTE ALKYL ETHERS AND SUBSTITUTE PHENYLICS AND THEIR PREPARATION METHODS |
| DE19752524865 DE2524865A1 (en) | 1974-06-04 | 1975-06-04 | ALKYL ETHERS SUBSTITUTED BY SUBSTITUTED PHENYL, THE METHOD OF MANUFACTURING THEM AND THE PHARMACEUTICAL PRODUCTS CONTAINING THEM |
| AU81855/75A AU8185575A (en) | 1974-06-04 | 1975-06-04 | Substituted-phenyl substituted-alkyl ethers and the prep- aration thereof |
| CH719775A CH613940A5 (en) | 1974-06-04 | 1975-06-04 | Process for the preparation of alkyl ethers substituted by substituted phenyl |
| CA228,557A CA1050985A (en) | 1974-06-04 | 1975-06-04 | Substituted-phenyl substituted-alkyl ethers and the preparation thereof |
| AT125178A AT352705B (en) | 1974-06-10 | 1978-02-21 | PROCESS FOR THE PREPARATION OF NEW AMINO ALKYLPHENOXYALCANIC ACIDS AND THEIR ESTERS AND SALT |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2786975A JPS6025425B2 (en) | 1975-03-06 | 1975-03-06 | Synthesis method of substituted phenoxy fatty acids |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS51101977A JPS51101977A (en) | 1976-09-08 |
| JPS6025425B2 true JPS6025425B2 (en) | 1985-06-18 |
Family
ID=12232891
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2786975A Expired JPS6025425B2 (en) | 1974-06-04 | 1975-03-06 | Synthesis method of substituted phenoxy fatty acids |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6025425B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA009374B1 (en) * | 2003-09-03 | 2007-12-28 | Кова Ко., Лтд. | Ppar-activating compound and pharmaceutical composition containing same |
-
1975
- 1975-03-06 JP JP2786975A patent/JPS6025425B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS51101977A (en) | 1976-09-08 |
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