JPS5819662B2 - Method for producing 2↓-hydroxy↓-3↓-butenoic acid derivative - Google Patents
Method for producing 2↓-hydroxy↓-3↓-butenoic acid derivativeInfo
- Publication number
- JPS5819662B2 JPS5819662B2 JP9450678A JP9450678A JPS5819662B2 JP S5819662 B2 JPS5819662 B2 JP S5819662B2 JP 9450678 A JP9450678 A JP 9450678A JP 9450678 A JP9450678 A JP 9450678A JP S5819662 B2 JPS5819662 B2 JP S5819662B2
- Authority
- JP
- Japan
- Prior art keywords
- medoxy
- hydroxy
- naphthyl
- methyl
- water
- 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
- 238000004519 manufacturing process Methods 0.000 title description 2
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 claims description 11
- 229910001623 magnesium bromide Inorganic materials 0.000 claims description 11
- -1 glycidic acid ester Chemical class 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- VBWPSWWDYVWZKA-UHFFFAOYSA-N 2-hydroxybut-3-enoic acid Chemical class C=CC(O)C(O)=O VBWPSWWDYVWZKA-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 238000000921 elemental analysis Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- APQIUTYORBAGEZ-UHFFFAOYSA-N 1,1-dibromoethane Chemical compound CC(Br)Br APQIUTYORBAGEZ-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- IMTBHSQAGDZTQC-UHFFFAOYSA-N butyl but-3-enoate Chemical group CCCCOC(=O)CC=C IMTBHSQAGDZTQC-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- XSAYZAUNJMRRIR-UHFFFAOYSA-N 2-acetylnaphthalene Chemical compound C1=CC=CC2=CC(C(=O)C)=CC=C21 XSAYZAUNJMRRIR-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- SLUNEGLMXGHOLY-UHFFFAOYSA-N benzene;hexane Chemical compound CCCCCC.C1=CC=CC=C1 SLUNEGLMXGHOLY-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- VKCNNDPZFOVURD-UHFFFAOYSA-N 2-naphthalen-1-ylpropanoic acid Chemical compound C1=CC=C2C(C(C(O)=O)C)=CC=CC2=C1 VKCNNDPZFOVURD-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- PVEOYINWKBTPIZ-UHFFFAOYSA-M but-3-enoate Chemical compound [O-]C(=O)CC=C PVEOYINWKBTPIZ-UHFFFAOYSA-M 0.000 description 1
- YJRGMUWRPCPLNH-UHFFFAOYSA-N butyl 2-chloroacetate Chemical group CCCCOC(=O)CCl YJRGMUWRPCPLNH-UHFFFAOYSA-N 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 150000002168 ethanoic acid esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 150000004715 keto acids Chemical class 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- UBCJCAPLMBHKPY-UHFFFAOYSA-L magnesium;oxolane;dibromide Chemical compound [Mg+2].[Br-].[Br-].C1CCOC1 UBCJCAPLMBHKPY-UHFFFAOYSA-L 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- WQKGAJDYBZOFSR-UHFFFAOYSA-N potassium;propan-2-olate Chemical compound [K+].CC(C)[O-] WQKGAJDYBZOFSR-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 description 1
- WBQTXTBONIWRGK-UHFFFAOYSA-N sodium;propan-2-olate Chemical compound [Na+].CC(C)[O-] WBQTXTBONIWRGK-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】 体の製造法に関する。[Detailed description of the invention] Concerning body manufacturing methods.
本発明によれば、一般式
（式中Ｒは低級アルキル基を示す）で表わされるグリシ
ド酸エステル誘導体を臭化マグネシウムで処理すること
により一般式
（式中Ｒは低級アルキル基を示す）で表わされる化合物
が良好な収率で得られる。According to the present invention, by treating a glycidic acid ester derivative represented by the general formula (in which R represents a lower alkyl group) with magnesium bromide, the glycidic acid ester derivative represented by the general formula (in the formula, R represents a lower alkyl group) The compound is obtained in good yield.
本発明方法における臭化マグネシウムの使用量は原料化
合物に対して０．５〜３倍モル程度であるが、操作上原
料１モルに対して１．０〜１．２モル程度使用すると極
めて高収率で目的物を得ることができる。The amount of magnesium bromide used in the method of the present invention is about 0.5 to 3 times the mole of the raw material compound, but for operational reasons, if it is used about 1.0 to 1.2 moles per mole of the raw material, the yield is extremely high. You can get what you want at a reasonable rate.
反応にあたっては、実質上水分の不存在下で実施すべき
であるが、無水の溶媒は使用してよく、例えば、テトラ
ヒドロフラン、ジオキサン、イソプロビルエーテル等の
エーテル類、酢酸メチル、酢酸エチル、酢酸ブチル等の
酢酸エステル類、ベンゼン、トルエン、キシレン等の芳
香族炭化水素類、塩化メチレン、クロロホルム、四塩化
炭素等のハロゲン化炭素類、ジメチルホルムアミド、ジ
メチルアセトアミド、ホルムアミド等のアミド類等の溶
媒があげられる。The reaction should be carried out in the substantial absence of water, but anhydrous solvents may be used, for example, ethers such as tetrahydrofuran, dioxane, isopropyl ether, methyl acetate, ethyl acetate, butyl acetate. Solvents include acetic acid esters such as benzene, toluene, xylene, etc., halogenated carbons such as methylene chloride, chloroform, carbon tetrachloride, amides such as dimethylformamide, dimethylacetamide, formamide, etc. It will be done.
反応温度は０〜１２０℃の間で支障なく行い得るが、２
０〜８０℃を採用するのが便である。The reaction temperature can be carried out without any problem between 0 and 120°C, but 2
It is convenient to use a temperature of 0 to 80°C.
反応時間は３０分間ないし２０時間であるが、大体２〜
４時間程度で実質上反応は完結できる。The reaction time is 30 minutes to 20 hours, but generally 2 to 20 hours.
The reaction can be substantially completed in about 4 hours.
臭化マグネシウムは通常有機溶媒中で金属マグネシウム
とジブロムエタンのごときとの反応により生成されたも
のをそのまま懸濁液の状態で直ちに使用するのが特に好
適である。It is particularly preferable that magnesium bromide is produced by the reaction of magnesium metal with dibromoethane or the like in an organic solvent and used immediately in the form of a suspension.
このようにして得られる本発明方法の生成物は、ナプロ
キセンとして知られる既知の消炎剤の中間体として有用
である。The product of the process of the invention thus obtained is useful as an intermediate for the known anti-inflammatory agent known as naproxen.
すなわち得られた前記式（ＩＩ）の２−ヒドロキシ−３
−ブテン酸誘導体を例えばメタノール中ナトリウムメチ
ラートで処理した後、加水分解して式
のケト酸とし、ついでアルカリ中過酸化水素で処理して
式
の２−（６−メドキシー２−ナフチル）−プロピオン酸
を得ることができる。That is, the obtained 2-hydroxy-3 of formula (II)
- Butenoic acid derivatives are treated with e.g. sodium methylate in methanol and then hydrolyzed to give the keto acids of the formula and then treated with hydrogen peroxide in alkali to give the 2-(6-medoxy-2-naphthyl)-propion of the formula Acid can be obtained.
本発明方法における原料として使用される前記式（１）
で示される化合物は、例えば式
酢酸エステルと反応させることにより製造することがで
き、この反応はダルツエン縮合の条件下すなわち不活性
ガス下において塩基の縮合剤を存在させ、無水条件下で
行うことが好ましい。The above formula (1) used as a raw material in the method of the present invention
A compound of the formula can be prepared, for example, by reaction with an acetate of the formula, and this reaction can be carried out under anhydrous conditions in the presence of a basic condensing agent under the conditions of Dalzene condensation, that is, under an inert gas. preferable.
縮合剤としてはナトリウムメトキシド、ナトリウムエト
キシド、ナトリウムイソプロポキシド、カリウムイソプ
ロポキシド、カリウム第３級ブトキシドを用いることが
できる。As the condensing agent, sodium methoxide, sodium ethoxide, sodium isopropoxide, potassium isopropoxide, and potassium tertiary butoxide can be used.
次に本発明方法による実施例を掲げる。Next, examples using the method of the present invention are listed.
ただし本発明はこれらにより限定されるものではない。However, the present invention is not limited to these.
実施例 １
２−ヒドロキシ−３−（６−メドキシー２−ナフチル）
−３−ブテン酸メチル
６−メドキシー２−アセチルナフクレン１２０ｇおよび
クロル酢酸メチル１２０ｇをトルエン１２００ｍ１に溶
解させ、撹拌しながらカリウム第３級ブチラード１２０
ｇを窒素気流中３〜５℃で２時間を要して徐々に加えた
。Example 1 2-hydroxy-3-(6-medoxy-2-naphthyl)
-Methyl 3-butenoate 120 g of 6-medoxy-2-acetylnafculene and 120 g of methyl chloroacetate were dissolved in 1200 ml of toluene, and while stirring, 120 g of potassium tertiary butyrad was dissolved.
g was gradually added over a period of 2 hours at 3-5° C. in a nitrogen stream.
５〜７℃で１時間撹拌した抜水および酢酸エチルを加え
そして充分撹拌した。Drained water and ethyl acetate, which had been stirred at 5-7°C for 1 hour, were added and stirred thoroughly.
有機層を分取し、水洗した後無水硫酸ナトリウムで乾燥
した。The organic layer was separated, washed with water, and then dried over anhydrous sodium sulfate.
有機溶媒を減圧留去し、得られる粗結晶をベンゼンから
再結晶して３−メチル−３−（６−メドキシー２−ナフ
チル）−グリシド酸メチル１２０ｇを得た。The organic solvent was distilled off under reduced pressure, and the resulting crude crystals were recrystallized from benzene to obtain 120 g of methyl 3-methyl-3-(6-medoxy-2-naphthyl)-glycidate.
収率７３．５％（理論値）、融点１２０．１〜１２４．
３℃。Yield 73.5% (theoretical value), melting point 120.1-124.
3℃.
Ｃ１６Ｈ１６０４として元素分析結果は次のとおりであ
る。The elemental analysis results for C16H1604 are as follows.
金属マグネシウム８．８ｇ、ジブロムエタン６８ｇおよ
びテトラヒドロフラン２３０ｍ１から臭化マグネシウム
を調製した。Magnesium bromide was prepared from 8.8 g of magnesium metal, 68 g of dibromoethane and 230 ml of tetrahydrofuran.
この撹拌された懸濁液に、上述のようにして製造した３
−メチル−３−（６−メドキシー２−ナフチル）−グリ
シド酸メチル８３ｇをトルエン５００ｍ１に溶解させ、
２５〜３５°Ｃで３０分間を要して滴下した。To this stirred suspension was added 3
- 83 g of methyl-3-(6-medoxy-2-naphthyl)-glycidate was dissolved in 500 ml of toluene,
The dropwise addition took 30 minutes at 25-35°C.
滴下終了後２０〜２５°Ｃで２時間撹拌し、反応液を希
塩酸中に注いだ。After the dropwise addition was completed, the mixture was stirred at 20 to 25°C for 2 hours, and the reaction solution was poured into dilute hydrochloric acid.
有機層を分取し、水、重炭酸ソーダ水溶液、水および飽
和食塩水で順次洗い、無水硫酸マグネシウムで乾燥した
。The organic layer was separated, washed successively with water, aqueous sodium bicarbonate solution, water and saturated brine, and dried over anhydrous magnesium sulfate.
トルエンを減圧留去し、残渣をベンゼン−ヘキサンから
再結晶して２−ヒドロキシ−３−（６−メドキシー２−
ナフチル）−３−ブテン酸メチル７５ｇを得た。Toluene was distilled off under reduced pressure, and the residue was recrystallized from benzene-hexane to give 2-hydroxy-3-(6-medoxy-2-
75 g of methyl naphthyl-3-butenoate was obtained.
収率９０．３％（理論値）、融点９０．６〜９２．５°
ＣＯＣｌ６Ｈ１６０４として元素分析結果は次のとおり
である。Yield 90.3% (theoretical value), melting point 90.6-92.5°
The elemental analysis results for COCl6H1604 are as follows.
実施例 ２
２−ヒドロキシ−３−（６−メドキシー２−すメチル）
−３−ブテン酸第３級ブチル
６−メドキシー２−アセチルナフタレン５．５ｇおよび
クロル酢酸第３級ブチル８．３ｇをトルエン６０ＴｒＬ
ｌに溶解させ、撹拌しながらカリウム第３級ブチルー１
−６．２９を０〜５℃で４０分間をかけて徐々に加えた
。Example 2 2-hydroxy-3-(6-medoxy-2-sumethyl)
- Tertiary butyl 3-butenoate 5.5 g of 6-medoxy-2-acetylnaphthalene and 8.3 g of tertiary butyl chloroacetate were added to 60 Tr of toluene.
Potassium tert-butyl
-6.29 was gradually added over 40 minutes at 0-5°C.
０〜５°Ｃで１時間撹拌した後、水および酢酸エチルを
加えそして充分撹拌した。After stirring for 1 hour at 0-5°C, water and ethyl acetate were added and stirred well.
有機層を分取し、水洗しそして無水硫酸ナトＩＪウムで
乾燥した。The organic layer was separated, washed with water, and dried over anhydrous sodium sulfate.
有機溶媒を減圧留去して半結晶状の３−メチル−３−（
６−メドキシー２−ナフチル）−グリシド酸第３級ブチ
ル９．１ｇを得た。The organic solvent was distilled off under reduced pressure to obtain semicrystalline 3-methyl-3-(
9.1 g of tertiary butyl 6-medoxy (2-naphthyl)-glycidate was obtained.
収率は定量的であった。The yield was quantitative.
Ｃ１９Ｈ２２０４として元素分析結果は次のとおりであ
る。The elemental analysis results for C19H2204 are as follows.
金属マグネシウム０．４，９．ジブロムエタン３．３ｇ
およびテトラヒドロフラン３０７ｒＬｌから臭化マグネ
シウムを調製した。Metal magnesium 0.4,9. Dibromoethane 3.3g
Magnesium bromide was prepared from 307 rLl of tetrahydrofuran.
この撹拌懸濁液に、上述のように製造した３−メチル−
３−（６−メドキシー２−ナフチル）−グリシド酸第３
級ブチル３゜６ｙをイソプロピルエーテル２０ｍ１に溶
解させ、２５〜３０°Ｃで５分間を要して滴下した。To this stirred suspension was added 3-methyl-
3-(6-medoxy-2-naphthyl)-glycidic acid tertiary
3.6y of butyl was dissolved in 20 ml of isopropyl ether and added dropwise over 5 minutes at 25-30°C.
滴下終了後２０〜２５℃で１時間撹拌し、反応液を希塩
酸中に注いだ。After the dropwise addition was completed, the mixture was stirred at 20 to 25°C for 1 hour, and the reaction solution was poured into dilute hydrochloric acid.
イソプロピルエーテルで抽出を行い、抽出液を水、重炭
酸ソーダ水溶液、水および飽和食塩水で順次洗い、そし
て無水硫酸マグネシウムで乾燥した。Extraction was performed with isopropyl ether, and the extract was washed successively with water, an aqueous sodium bicarbonate solution, water, and saturated brine, and dried over anhydrous magnesium sulfate.
溶媒を減圧留去し、残渣をベンゼン−ヘキサンから再結
晶して２−ヒドロキシ−３−（６−メドキシー２−ナフ
チル）−３−ブテン酸第３級ブチル３．３ｇを得た。The solvent was distilled off under reduced pressure, and the residue was recrystallized from benzene-hexane to obtain 3.3 g of tertiary butyl 2-hydroxy-3-(6-medoxy-2-naphthyl)-3-butenoate.
融点８５．７〜８６．４℃、収率９２％（理論値）。Melting point: 85.7-86.4°C, yield: 92% (theoretical value).
Ｃ１９Ｈ２□０４として元素分析結果は次のとおりであ
る。The elemental analysis results for C19H2□04 are as follows.
実施例 ３
２−ヒドロキシ−３−（６−メドキシー２−ナフチル）
−３−ブテン酸第３級ブチル
３−メチル−３−（６−メドキシー２−ナフチル）−グ
リシド酸第３級ブチル６．３ｇを酢酸エチル７０ＴｒＬ
ｌに溶解させ、臭化マグネシウム３．７ｇを加え２５〜
３０℃で２時間撹拌した。Example 3 2-hydroxy-3-(6-medoxy-2-naphthyl)
- Tertiary butyl 3-butenoate 6.3 g of tertiary butyl 3-methyl-3-(6-medoxy-2-naphthyl)-glycidate was added to 70 TrL of ethyl acetate.
1, add 3.7 g of magnesium bromide, and add 25~
The mixture was stirred at 30°C for 2 hours.
反応液に希塩酸を加え、酢酸エチルで抽出した。Dilute hydrochloric acid was added to the reaction solution, and the mixture was extracted with ethyl acetate.
抽出液を水および飽和食塩水で順次洗い、無水硫酸ナト
リウムで乾燥した。The extract was washed successively with water and saturated brine, and dried over anhydrous sodium sulfate.
酢酸エチルを減圧留去して２−ヒドロキシ−３−（６−
メドキシー２−ナフチル）−３−ブテン酸第３級ブチル
６．１ｇを得た。Ethyl acetate was distilled off under reduced pressure to give 2-hydroxy-3-(6-
6.1 g of tertiary butyl medoxy-2-naphthyl)-3-butenoate was obtained.
融点８５．７〜８６．４℃、収率９６．８％（理論値）
。Melting point: 85.7-86.4°C, yield: 96.8% (theoretical value)
.
実施例 ４
２−ヒドロキシ−３−（６−メドキシー２−ナフチル）
−３−ブテン酸メチル
３−メチル−３−（６−ノドキシ−２〜ナフチル）−ク
リシト酸メチル２７．２ｊｉをクロロホルム３００ｒｒ
Ｌｌに溶解させ、臭化マグネシウム１８．４ｇを加え２
０〜２５°Ｃで２時間撹拌した。Example 4 2-hydroxy-3-(6-medoxy-2-naphthyl)
-Methyl 3-butenoate 27.2ji of methyl 3-methyl-3-(6-nodoxy-2-naphthyl)-crisitate was added to 300rr of chloroform.
Dissolve in Ll, add 18.4g of magnesium bromide and add 2
Stirred at 0-25°C for 2 hours.
希塩酸を加えた後クロロホルムで抽出した。After adding dilute hydrochloric acid, the mixture was extracted with chloroform.
抽出液を水および飽和食塩水で順次洗い、無水硫酸マグ
ネシウムで乾燥した。The extract was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate.
溶媒を減圧留去して２−ヒドロキシ−３−（６−メドキ
シー２−ナフチル）−３−ブテン酸メチル２６．４ｇを
得た。The solvent was distilled off under reduced pressure to obtain 26.4 g of methyl 2-hydroxy-3-(6-medoxy-2-naphthyl)-3-butenoate.
融点９０．６〜９２．５℃、収率９７．６％（理論値）
。Melting point 90.6-92.5℃, yield 97.6% (theoretical value)
.
実施例 ５
２−ヒドロキシ−３−（６−メドキシー２−ナフチル）
−３−ブテン酸第３級ブチル
３−メチル−３−（６−メドキシー２−ナフチル）−グ
リシド酸第３級ブチル３１．４．９をベンゼン１０１０
０Ｏに溶解させ、臭化マグネシウム１８．４ｇを加え、
２５〜３０℃で３時間撹拌した。Example 5 2-hydroxy-3-(6-medoxy-2-naphthyl)
Tertiary butyl 3-butenoate 3-methyl-3-(6-medoxy-2-naphthyl)-tertiary butyl glycidate 31.4.9 to benzene 1010
Dissolve in 0O, add 18.4g of magnesium bromide,
Stirred at 25-30°C for 3 hours.
反応液に希塩酸を加え、ベンゼン抽出を行った。Dilute hydrochloric acid was added to the reaction solution, and benzene extraction was performed.
抽出液を水および飽和食塩水で順次洗い、無水硫酸ナト
リウムで乾燥した。The extract was washed successively with water and saturated brine, and dried over anhydrous sodium sulfate.
溶媒を減圧下に留去し、残渣ヲペンゼンーヘキサンから
再結晶して２−ヒドロキシ−３−（６−メドキシー２−
ナフチル）−３−ブテン酸第３級ブチル２９．２ｇを得
た。The solvent was distilled off under reduced pressure, and the residue was recrystallized from penzene-hexane to give 2-hydroxy-3-(6-medoxy-2-
29.2 g of tertiary butyl (naphthyl)-3-butenoate was obtained.
融点８５．７〜８６．４°Ｃ１収率９３，０％（理論値
）。Melting point 85.7-86.4° C1 Yield 93.0% (theoretical value).
実施例 ６
２−ヒドロキシ−３−（６−メドキシー２−ナフチル）
−３−ブテン酸メチル
３−メチル−３−（６−メドキシー２−ナフチル）−グ
リシド酸メチル６．３ｇをジメチルホルムアミド５０ｍ
１に溶解させ、臭化マグネシウム４．２Ｉを加え、２０
〜２５℃で２時間撹拌した。Example 6 2-hydroxy-3-(6-medoxy-2-naphthyl)
-Methyl 3-butenoate 6.3 g of 3-methyl-3-(6-medoxy-2-naphthyl)-methyl glycidate was dissolved in 50 m of dimethylformamide.
1, add 4.2I of magnesium bromide, and add 20
Stir at ~25°C for 2 hours.
反応液を希塩酸中に注ぎ、酢酸エチルで抽出した。The reaction solution was poured into diluted hydrochloric acid and extracted with ethyl acetate.
抽出液を水および飽和食塩水で順次洗い、無水硫酸ナト
リウムで乾燥した。The extract was washed successively with water and saturated brine, and dried over anhydrous sodium sulfate.
溶媒を減圧留去し２−ヒドロキシ−３−（６−メドキシ
ー２−ナフチル）＝３−ブテン酸メチル５．７ｇを得た
。The solvent was distilled off under reduced pressure to obtain 5.7 g of methyl 2-hydroxy-3-(6-medoxy-2-naphthyl) 3-butenoate.
融点９０．６〜９２．５℃、収率９０％（理論値）。Melting point: 90.6-92.5°C, yield: 90% (theoretical value).
実施例 ７
２−（６−メドキシー２−ナフチル）−プロピオン酸
６−メドキシー２−アセチルナフタレン１２０ｇおよび
クロル酢酸メチル１２０ｇをトルエン１２００ｍ１に溶
解させ、撹拌しながらカリウム第３級ブチラード１２０
ｇを３〜５℃で２時間を要して徐々に加えた。Example 7 2-(6-Medoxy-2-naphthyl)-propionic acid 120 g of 6-medoxy-2-acetylnaphthalene and 120 g of methyl chloroacetate are dissolved in 1200 ml of toluene and, with stirring, 120 g of potassium tertiary butylade is added.
g was gradually added over a period of 2 hours at 3-5°C.
５〜７℃で１時間撹拌した後、水および酢酸エチルを加
えそして充分撹拌を行った。After stirring at 5-7°C for 1 hour, water and ethyl acetate were added and the mixture was thoroughly stirred.
有機層を分取し、水および飽和食塩水で順次洗い、無水
硫酸す） ＩＪウムで乾燥した。The organic layer was separated, washed successively with water and saturated brine, and dried over anhydrous sulfuric acid.
有機溶媒を減圧留去してグリシド酸エステルの粗結晶１
６６．３ｇを得た。The organic solvent was distilled off under reduced pressure to obtain crude crystals of glycidic acid ester 1.
66.3g was obtained.
エチレンジプロミド１３５ｐ、マグネシウム１７．５ｆ
ｌおよびテトラヒドロフラン３１０ＴＬｌとから臭化マ
グネシウムテトラヒドロフラン液を調製した。Ethylene dipromide 135p, magnesium 17.5f
A magnesium bromide tetrahydrofuran solution was prepared from 310 TL of magnesium bromide and 310 TL of tetrahydrofuran.
このテトラヒドロフラン液をトルエン４００ＴＬｌで希
釈し、撹拌しながら２５〜３０℃で、上記の粗結晶１６
６．３．９をトルエン６００ｍ１に溶解した溶液に３０
分間を要して滴下した。This tetrahydrofuran solution was diluted with 400 TLl of toluene, and heated at 25 to 30°C with stirring to obtain the above crude crystal 16.
6.3.9 in a solution of 600 ml of toluene.
It took several minutes to drip.
２０〜２５℃で２時間撹拌した後１０〜１５°Ｃに冷却
し、３５％塩酸６５ｍ１を水５’００ｍ１で希釈して１
時間を要して滴下した。After stirring at 20-25°C for 2 hours, the mixture was cooled to 10-15°C, and 65ml of 35% hydrochloric acid was diluted with 5'00ml of water.
It took some time to drip.
滴下終了後１５分間撹拌し、有機層を分取した。After the dropwise addition was completed, the mixture was stirred for 15 minutes and the organic layer was separated.
有機層を水、重炭酸ナトリウム水溶液、水および飽和食
塩水で順次洗い、無水硫酸ナトリウムで乾燥した。The organic layer was washed successively with water, aqueous sodium bicarbonate, water and saturated brine, and dried over anhydrous sodium sulfate.
溶媒を減圧下に留去してヒドロキシブテン酸エステルの
粗結晶１５８．６ｇを得た。The solvent was distilled off under reduced pressure to obtain 158.6 g of crude crystals of hydroxybutenoic acid ester.
上記の粗結晶１５８．６ｇをトルエン１． ＯＯＯＴＬ
ｌに溶解させ、これに２８％ナトリウムメチラートメタ
ノール溶液１８０ｍ１を加え、５４〜５６℃で１時間撹
拌した。158.6 g of the above crude crystals were mixed with 1.5 g of toluene. OOOTL
180 ml of 28% sodium methylate methanol solution was added thereto, and the mixture was stirred at 54-56°C for 1 hour.
ついで５０〜５５°Ｃで水６００ｍ１を加え、３０分間
撹拌した。Then, 600 ml of water was added at 50-55°C and stirred for 30 minutes.
反応液を１５〜１７℃に冷却し、撹拌しながら３０％過
酸化水素水９０ｍ１を３０分間を要して滴下した。The reaction solution was cooled to 15 to 17° C., and 90 ml of 30% hydrogen peroxide solution was added dropwise over 30 minutes while stirring.
滴下終了後１５〜２０℃で１時間撹拌し、水層を分取し
た。After the dropwise addition was completed, the mixture was stirred at 15 to 20°C for 1 hour, and the aqueous layer was separated.
この水溶液に３５％塩酸９０ｍ１を加えて酸性とし、次
いで酢酸エチルで抽出した。This aqueous solution was made acidic by adding 90 ml of 35% hydrochloric acid, and then extracted with ethyl acetate.
抽出液を水および飽和食塩水で順次洗い、無水硫酸ナト
リウムで乾燥した。The extract was washed successively with water and saturated brine, and dried over anhydrous sodium sulfate.
酢酸エチルを減圧留去し、得られる粗結晶をイソプロピ
ルアルコールから再結晶して２−（６−メドキシー２−
ナフチル）−プロピオン酸８８ｇを得た。Ethyl acetate was distilled off under reduced pressure, and the resulting crude crystals were recrystallized from isopropyl alcohol to give 2-(6-medoxy 2-
88 g of (naphthyl)-propionic acid were obtained.
融点１５２．０〜１５４．１°Ｃ１収率６３．７％（６
−メドキシー２−アセチルナフタレンからの理論収率）
。Melting point 152.0-154.1°C1 Yield 63.7% (6
-Theoretical yield from medoxy 2-acetylnaphthalene)
.
Ｃ１４Ｈ１４０３として元素分析結果は次のとおりであ
る。The elemental analysis results for C14H1403 are as follows.
Claims (1)
ド酸エステル誘導体を臭化マグネシウムで処理すること
を特徴とする、一般式 （式中Ｒは低級アルキル基を示す）で表わされる２−ヒ
ドロキシ−３−ブテン酸誘導体の製造法３[Scope of Claims] 1. A glycidic acid ester derivative represented by the general formula (in which R represents a lower alkyl group) is treated with magnesium bromide. Method 3 for producing a 2-hydroxy-3-butenoic acid derivative represented by
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9450678A JPS5819662B2 (en) | 1978-08-04 | 1978-08-04 | Method for producing 2↓-hydroxy↓-3↓-butenoic acid derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9450678A JPS5819662B2 (en) | 1978-08-04 | 1978-08-04 | Method for producing 2↓-hydroxy↓-3↓-butenoic acid derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5522613A JPS5522613A (en) | 1980-02-18 |
| JPS5819662B2 true JPS5819662B2 (en) | 1983-04-19 |
Family
ID=14112192
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9450678A Expired JPS5819662B2 (en) | 1978-08-04 | 1978-08-04 | Method for producing 2↓-hydroxy↓-3↓-butenoic acid derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5819662B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6399550U (en) * | 1986-12-18 | 1988-06-28 |
-
1978
- 1978-08-04 JP JP9450678A patent/JPS5819662B2/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6399550U (en) * | 1986-12-18 | 1988-06-28 |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5522613A (en) | 1980-02-18 |
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