JPS582934B2 - Process for producing 2-(substituted aryl)-propionic acid - Google Patents

Process for producing 2-(substituted aryl)-propionic acid

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Publication number
JPS582934B2
JPS582934B2 JP49086005A JP8600574A JPS582934B2 JP S582934 B2 JPS582934 B2 JP S582934B2 JP 49086005 A JP49086005 A JP 49086005A JP 8600574 A JP8600574 A JP 8600574A JP S582934 B2 JPS582934 B2 JP S582934B2
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JP
Japan
Prior art keywords
water
acid
ethyl acetate
ether
extracted
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
Application number
JP49086005A
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Japanese (ja)
Other versions
JPS5116636A (en
Inventor
桂 木暮
憲義 末田
静夫 樋本
雄二郎 吉野
邦男 中川
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Nisshin Seifun Group Inc
Original Assignee
Nisshin Seifun Group Inc
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Filing date
Publication date
Application filed by Nisshin Seifun Group Inc filed Critical Nisshin Seifun Group Inc
Priority to JP49086005A priority Critical patent/JPS582934B2/en
Priority to DE19752533397 priority patent/DE2533397A1/en
Priority to GB3133775A priority patent/GB1521906A/en
Publication of JPS5116636A publication Critical patent/JPS5116636A/en
Publication of JPS582934B2 publication Critical patent/JPS582934B2/en
Expired legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/76—Unsaturated compounds containing keto groups
    • C07C59/90—Unsaturated compounds containing keto groups containing singly bound oxygen-containing groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
    • C07C45/57—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom
    • C07C45/58—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom in three-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/16—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation
    • C07C51/285—Preparation of carboxylic acids or their salts, halides or anhydrides by oxidation with peroxy-compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/30—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/30—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings
    • C07C57/38—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings polycyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/46—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
    • C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
    • C07C57/58—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
    • C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
    • C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
    • C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
    • C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
    • C07C59/68—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/76—Unsaturated compounds containing keto groups
    • C07C59/84—Unsaturated compounds containing keto groups containing six membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/76—Unsaturated compounds containing keto groups
    • C07C59/86—Unsaturated compounds containing keto groups containing six-membered aromatic rings and other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/76—Unsaturated compounds containing keto groups
    • C07C59/88—Unsaturated compounds containing keto groups containing halogen

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Description

【発明の詳細な説明】 本発明は消炎剤として有用な２−（置換アリール）−プ
ロピオン酸化合物の新規な製造法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing 2-(substituted aryl)-propionic acid compounds useful as anti-inflammatory agents.

本発明によれば、一般式 （式中Ｒ１は４−低級アルキルフエニル、４−ビフエニ
リル、４−シクロへキシルフエニル、３５−フエノキシ
フエニルまたは４′−フルオロ−４−ビフエニリル基で
ある）を有する置換アリールピルビン酸が酸化されて一
般式 （式中Ｒ１は前記と同様である）を有する置換アリール
プロピオン酸が生成される。According to the invention, the general formula (wherein R1 is a 4-lower alkylphenyl, 4-biphenylyl, 4-cyclohexylphenyl, 35-phenoxyphenyl or 4'-fluoro-4-biphenylyl group) The substituted arylpyruvate having the formula is oxidized to produce the substituted arylpropionic acid having the general formula (wherein R1 is as defined above).

本発明方法により得られる化合物は消炎剤として興味あ
るものである。The compounds obtained by the process of the invention are of interest as anti-inflammatory agents.

従来この種の化合物としてはイブプロフエンが代表的で
あり、その合成について種々の報告がなされている。Conventionally, ibuprofen has been a typical example of this type of compound, and various reports have been made regarding its synthesis.

しかしながら本発明におけるようなケト酸構造の化合物
を酸化剤で処理して支障なく目的物を得ることについて
は全く知られていない。However, it is not known at all that a compound having a keto acid structure can be treated with an oxidizing agent to obtain the desired product without any problems as in the present invention.

本発明によればかかる酸化剤処理工程を確立することに
より入手容易なグリシド酸エステルから出発して極めて
良好且つ安定した収率で目的物に到達し得る方法を可能
ならしめるものである。According to the present invention, by establishing such an oxidizing agent treatment step, it is possible to obtain a target product in an extremely good and stable yield starting from an easily available glycidic acid ester.

本発明による一般式（Ｉ）の化合物の酸化は過酸化水素
、有機過酸（過酢酸、過ぎ酸）、過マンガン酸カリのよ
うな酸化剤が用いられる。For the oxidation of the compound of general formula (I) according to the present invention, oxidizing agents such as hydrogen peroxide, organic peracids (peracetic acid, peracid), and potassium permanganate are used.

溶媒としてはアルカリ水溶液、有機酸、アセトンなどが
あげられる。Examples of the solvent include aqueous alkaline solutions, organic acids, and acetone.

使用溶媒の種類は一般に酸化剤の種類に依存し、当業者
には自明のように過酢酸／酢酸、過ぎ酸／ぎ酸、過酸化
水素／アルカリ水溶液そして過マンガン酸カリ／アセト
ンのような組合せが好適である。The type of solvent used will generally depend on the type of oxidizing agent and will be obvious to those skilled in the art, including combinations such as peracetic acid/acetic acid, peracid/formic acid, hydrogen peroxide/aqueous alkali, and potassium permanganate/acetone. is suitable.

場合によりカルボン酸エステル基のけん化を起すような
酸化反応媒体が用いられるときは、一般式（Ｉ）の置換
アリールピルビン酸に代えてその低級アルキルエステル
を直接原料として使用して反応系中で遊離の酸を生せし
めることも可能である。In some cases, when an oxidation reaction medium that causes saponification of the carboxylic acid ester group is used, the lower alkyl ester of the substituted arylpyruvic acid of general formula (I) can be directly used as a raw material to free the carboxylic acid ester group in the reaction system. It is also possible to produce acids of

反応温度は１０ないし５０℃程度であり、反応時間は１
０〜１２０時間で充分である。The reaction temperature is about 10 to 50°C, and the reaction time is 1
0 to 120 hours is sufficient.

また本発明の原料化合物の製造にあたって相当するグリ
シド酸エステルを含水条件下で酸処理する場合は一般式
（ＩＩ）の化合物と一般式 （式中Ｒ１は前記と同様である）（ＩＩＩ）の化合物と
が反応混合物中に生成するが、これらは単離して本発明
方法に付することかできる。In addition, when the corresponding glycidic acid ester is acid-treated under hydrous conditions in the production of the raw material compound of the present invention, a compound of general formula (II) and a compound of general formula (III) (wherein R1 is the same as above) are used. are formed in the reaction mixture, which can be isolated and subjected to the process of the invention.

以下に本発明を更に説明するために実施例を掲げる。Examples are given below to further explain the present invention.

なお参考例１〜４は本発明の原料化合物の製造を例示す
るものである。Note that Reference Examples 1 to 4 illustrate the production of the raw material compounds of the present invention.

実施例 １ ２−（４−イソブチルフエニル）−プロピオン酸 ３−メチル−３−（４−イソブチルフエニル）−ピルビ
ン酸４．５ｇを８％水酸化ナトリウム水溶液４０ｍｌに
溶解させ、攪拌水冷を行いながら３０％過酸化水素水４
．０ｍｌを滴下した。Example 1 4.5 g of 3-methyl-3-(4-isobutylphenyl)-pyruvic acid 2-(4-isobutylphenyl)-propionate was dissolved in 40 ml of an 8% aqueous sodium hydroxide solution, and the mixture was stirred and cooled with water. while 30% hydrogen peroxide solution 4
．． 0 ml was added dropwise.

室温にもどして一夜攪拌を続け、不溶物はエーテル抽出
して除いた。The temperature was returned to room temperature, stirring was continued overnight, and insoluble materials were removed by extraction with ether.

抽出母液を塩酸酸性とし、エーテル抽出を行い、水洗乾
燥後エーテルを減圧留去し得られる粗結晶を石油ベンジ
ンから再結して２−（４−イソブチルフエニル）−プロ
ピオン酸３．２ｇを得た。The extracted mother liquor was made acidic with hydrochloric acid, extracted with ether, washed with water, and then dried, the ether was distilled off under reduced pressure, and the resulting crude crystals were recrystallized from petroleum benzine to obtain 3.2 g of 2-(4-isobutylphenyl)-propionic acid. Ta.

融点７５．０°〜７６．５℃、収率８０％（理論値）。Melting point 75.0°-76.5°C, yield 80% (theoretical value).

元素分析（Ｃ１３Ｈ１８Ｏ２として）結果は次のとおり
である。The elemental analysis (as C13H18O2) results are as follows.

理論値：Ｃ ７５．６９％ Ｈ８．８０％実測値：Ｃ
７５．５８％ Ｈ８．８３％実施例 ２ ２−（４−第３級プチルフエニル）一プロピオン酸 ３−メチル−３−（４−第３級プチルフエニル）−ピル
ビン酸９．０ｇを８％水酸化ナトリウム水溶液８０ｍｌ
に溶解させ、撹拌水冷を行いながら３０％過酸化水素水
８．０ｍｌを滴下した。Theoretical value: C 75.69% H8.80% Actual value: C
75.58% H8.83% Example 2 9.0 g of 3-methyl-3-(4-tertiary butylphenyl)-pyruvic acid 2-(4-tertiary butylphenyl) monopropionate was added to 8% sodium hydroxide. 80ml aqueous solution
8.0 ml of 30% hydrogen peroxide solution was added dropwise while stirring and cooling with water.

室温にもどして一夜攪拌を続け、不溶物はエーテル抽出
して除いた。The temperature was returned to room temperature, stirring was continued overnight, and insoluble materials were removed by extraction with ether.

抽出母液を塩酸酸性とし、エーテル抽出を行い、エーテ
ル層を水洗乾燥した後エーテルを減圧留去し、得られる
粗結晶を石油ベンジンから再結して２−（４一第３級プ
チルフエニル）一プロピオン酸６．４ｇを得た。The extracted mother liquor was acidified with hydrochloric acid, extracted with ether, the ether layer was washed with water and dried, the ether was distilled off under reduced pressure, and the resulting crude crystals were re-crystallized from petroleum benzene to obtain 2-(4-tertiary butylphenyl)-propion. 6.4 g of acid was obtained.

融点１００．６°〜１０２．４℃、収率８０％。Melting point: 100.6° to 102.4°C, yield: 80%.

元素分析（Ｃ１３Ｈ１８Ｏ２として）結果は次のとおり
である。The elemental analysis (as C13H18O2) results are as follows.

理論値：Ｃ ７５．６９％ Ｈ ８．８０％実測値：Ｃ
７５．５９％ Ｈ ８．７０％実施例 ３ ２−（４−シクロへキシルフエニル）−プロピオン酸 ３−メチル−３−（４−シクロへキシルフエニル）−ピ
ルビン酸１．１ｇを３％水酸化ナトリウム水溶液２０ｍ
ｌに溶解させ、攪拌水冷を行いながら３０％過酸化水素
水１．２ｍｌを滴下した。Theoretical value: C 75.69% H 8.80% Actual value: C
75.59% H 8.70% Example 3 1.1 g of 2-(4-cyclohexylphenyl)-propionate 3-methyl-3-(4-cyclohexylphenyl)-pyruvic acid was added to a 3% aqueous sodium hydroxide solution. 20m
1.2 ml of 30% hydrogen peroxide solution was added dropwise while stirring and cooling with water.

室温にもどして一夜攪拌を続け、不溶物はエーテル抽出
して除いた。The temperature was returned to room temperature, stirring was continued overnight, and insoluble materials were removed by extraction with ether.

抽出母液を塩酸で酸性とし、エーテル抽出を行い、エー
テル層を水洗乾燥した後エーテルを減圧留去し、得られ
る粗結晶をヘキサンから再結して２−（４−シクロへキ
シルフエニル）−プロピオン酸６５０ｍｇを得た。The extracted mother liquor was acidified with hydrochloric acid, extracted with ether, the ether layer was washed with water and dried, the ether was distilled off under reduced pressure, and the resulting crude crystals were recrystallized from hexane to give 2-(4-cyclohexylphenyl)-propionic acid. 650 mg was obtained.

融点１１０．０°〜１１１．９℃、収率６６％（理論値
）。Melting point 110.0°-111.9°C, yield 66% (theoretical value).

元素分析（Ｃ１５Ｈ２０Ｏ２として）結果は次のとおり
である。The elemental analysis (as C15H20O2) results are as follows.

理論値：Ｃ ７７．５５％ Ｈ ８．６８％実測値：Ｃ
７７．４９％ Ｈ ８．５６％実施例 ４ ２−（３−フエノキシフエニル）一プロピオン酸 ３−メチル−３−（３−フエノキシフエニル）−ピルビ
ン酸１．２ｇを３％水酸化ナトリウム水溶液２０ｍｌに
溶解させ、攪拌水冷を行いながら３０％過酸化水素水１
ｍｌを滴下した。Theoretical value: C 77.55% H 8.68% Actual value: C
77.49% H 8.56% Example 4 3% hydroxylation of 1.2 g of 3-methyl-3-(3-phenoxyphenyl)-pyruvic acid 2-(3-phenoxyphenyl) monopropionate Dissolve in 20 ml of sodium aqueous solution, add 1 ml of 30% hydrogen peroxide solution while stirring and cooling with water.
ml was added dropwise.

室温にもどして一夜攪拌を続け、不溶物はエーテル抽出
して除いた。The temperature was returned to room temperature, stirring was continued overnight, and insoluble materials were removed by extraction with ether.

抽出母液を塩酸酸性とし、エーテル抽出した。エーテル
層を水洗し、無水硫酸マグネシウムで乾燥した後エーテ
ルを減圧留去し無色油状の２−（３−フエノキシフエニ
ル）一プロピオン酸０．９ｇを得た。The extracted mother liquor was acidified with hydrochloric acid and extracted with ether. The ether layer was washed with water, dried over anhydrous magnesium sulfate, and the ether was distilled off under reduced pressure to obtain 0.9 g of 2-(3-phenoxyphenyl) monopropionic acid as a colorless oil.

収率８４％。元素分析（Ｃ１５Ｈ１４Ｏ３として）結果
は次のとおりである。Yield 84%. The elemental analysis (as C15H14O3) results are as follows.

理論値：Ｃ ７４．３６％ Ｈ ５．８３％実測値：Ｃ
７４．６１％ Ｈ ６．１０％実施例 ５ ２−（４−ビフエニリル）一プロピオン酸３−メチル−
３−（４−ビフエニリル）一ピルビン酸０．６ｇを３％
水酸化ナトリウム水溶液２０ｄに溶解させ、攪拌水冷を
行いながら３０％過酸化水素水１ｍｌを滴下した。Theoretical value: C 74.36% H 5.83% Actual value: C
74.61% H 6.10%Example 5 3-Methyl-2-(4-biphenylyl)monopropionate
0.6g of 3-(4-biphenylyl)monopyruvate at 3%
It was dissolved in 20 d of aqueous sodium hydroxide solution, and 1 ml of 30% hydrogen peroxide solution was added dropwise while stirring and cooling with water.

反応液を室温にもどし一夜攪拌を続け、不溶物は酢酸エ
チルで抽出して除いた。The reaction solution was returned to room temperature and stirred overnight, and insoluble materials were removed by extraction with ethyl acetate.

抽出母液を塩酸酸性とし、酢酸エチルで抽出した。The extracted mother liquor was acidified with hydrochloric acid and extracted with ethyl acetate.

酢酸エチル層を水洗し、無水硫酸マグネシウムで乾燥し
た後酢酸エチルを減圧留去し、得られる粗結晶をベンゼ
ンから再結して２−（４ービフエニリル）−プロピオン
酸０．４ｇを得た。The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, and then the ethyl acetate was distilled off under reduced pressure, and the resulting crude crystals were recrystallized from benzene to obtain 0.4 g of 2-(4-biphenylyl)-propionic acid.

融点１２２．９°〜１２４８℃、収率７５％（理論値）
。Melting point 122.9° to 1248°C, yield 75% (theoretical value)
.

元素分析（Ｃ１５Ｈ１４Ｏ２として）結果は次のとおり
である。The elemental analysis (as C15H14O2) results are as follows.

理論値：Ｃ ７９．６２％ Ｈ ６．２４％実測値：Ｃ
７９．５５％ Ｈ ６．３０％実施例 ６ ２−（４′−フルオロ−４−ビフエニリル）−プロピオ
ン酸 ３−メチル−３−（４′−フルオロ−４−ビフエニリル
）−ピルビン酸０．８ｇを３％水酸化ナトリウム水溶液
２０ｍｌに溶解させ、攪拌水冷を行いながら３０％過酸
化水素水１．０ｍｌを滴下した。Theoretical value: C 79.62% H 6.24% Actual value: C
79.55% H 6.30% Example 6 0.8 g of 3-methyl-3-(4'-fluoro-4-biphenylyl)-pyruvic acid 2-(4'-fluoro-4-biphenylyl)-propionic acid It was dissolved in 20 ml of 3% aqueous sodium hydroxide solution, and 1.0 ml of 30% hydrogen peroxide solution was added dropwise while stirring and cooling with water.

室温にもどして一夜攪拌し、不溶物は酢酸エチルで抽出
して除いた。The mixture was returned to room temperature and stirred overnight, and insoluble materials were removed by extraction with ethyl acetate.

抽出母液を塩酸酸性とし、酢酸エチルで抽出した。The extracted mother liquor was acidified with hydrochloric acid and extracted with ethyl acetate.

酢酸エチル層を水洗し、無水硫酸マグネシウムで乾燥し
た後酢酸エチルを減圧留去し、得られる粗結晶をベンゼ
ンから再結して２（４′−フルオロ−４−ビフエニリル
）−プロピオン酸０．５４ｇを得た。The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, and then the ethyl acetate was distilled off under reduced pressure. The resulting crude crystals were recrystallized from benzene to give 0.54 g of 2(4'-fluoro-4-biphenylyl)-propionic acid. I got it.

融点１４０．０°〜１４１．２℃、収率７５％（理論値
）。Melting point 140.0°-141.2°C, yield 75% (theoretical value).

元素分析（Ｃ１５Ｈ１３ＦＯ２として）結果は次のとお
りである。The elemental analysis (as C15H13FO2) results are as follows.

理論値：Ｃ ７３．７６％ Ｈ ５．３６％実測値：Ｃ
７３．７１％ Ｈ ５．３２％実施例 ７ ２−（４−イソブチルフエニル）−プロピオン酸 ３−メチル−３−（４−イソブチルフエニル）−ピルビ
ン酸２．３４ｇを氷酢酸２０ｍｌに溶解し、撹拌冷却し
ながら３０％過酸化水素水１０ｍｌを滴下した。Theoretical value: C 73.76% H 5.36% Actual value: C
73.71% H 5.32% Example 7 2-(4-isobutylphenyl)-propionate 2.34 g of 3-methyl-3-(4-isobutylphenyl)-pyruvic acid was dissolved in 20 ml of glacial acetic acid. 10 ml of 30% hydrogen peroxide solution was added dropwise while stirring and cooling.

室温にもどして１２０時間攪拌し、水中に注いだ。The mixture was returned to room temperature, stirred for 120 hours, and poured into water.

エーテル抽出し水洗した後無水硫酸マグネシウムで乾燥
し、エーテルを減圧留去し、得られる粗結晶を石油ベン
ジンから再結して２−（４−イソブチルフエニル）−プ
ロピオン酸１．６５ｇを得た。After extracting with ether and washing with water, it was dried over anhydrous magnesium sulfate, the ether was distilled off under reduced pressure, and the resulting crude crystals were recrystallized from petroleum benzine to obtain 1.65 g of 2-(4-isobutylphenyl)-propionic acid. .

融点７５．０°〜７６．５℃、収率８０％（理論値）。Melting point 75.0°-76.5°C, yield 80% (theoretical value).

実施例 ８ ２−（４−第３級プチルフエニル）−プロピオン酸 ３−メチル−３−（４−第３級プチルフエニル）−ピル
ビン酸４．６８ｇを氷酢酸４０ｍｌに溶解し、攪拌冷却
しながら３０％過酸化水素水１８ｍｌを滴下した。Example 8 4.68 g of 3-methyl-3-(4-tertiary butylphenyl)-pyruvic acid 2-(4-tertiary butylphenyl)-propionate was dissolved in 40 ml of glacial acetic acid, and the solution was dissolved to 30% while stirring and cooling. 18 ml of hydrogen peroxide solution was added dropwise.

室温にもどして４日間攪拌を続けた後、室温で反応液を
１／２に減圧濃縮し、水中に注いでエーテル抽出した。After returning to room temperature and continuing stirring for 4 days, the reaction solution was concentrated to 1/2 under reduced pressure at room temperature, poured into water, and extracted with ether.

エーテル層を水洗した後無水硫酸マグネシウムで乾燥し
た。The ether layer was washed with water and then dried over anhydrous magnesium sulfate.

エーテルを減圧留去し、得られる粗結晶を石油ベンジン
から再結して目的物３．１０ｇを得た。The ether was distilled off under reduced pressure, and the resulting crude crystals were recrystallized from petroleum benzene to obtain 3.10 g of the desired product.

融点１００．６°〜１０２．４℃、収率７５％（理論値
）。Melting point 100.6°-102.4°C, yield 75% (theoretical value).

実施例 ９ ２−（４−シクロへキシルフエニル）−プロピオン酸 ３−メチル−３−（４−シクロへキシルフエニル）−ピ
ルビン酸２．６１を氷酢酸２０ｍｌに溶解し、撹拌冷却
を行いながら３０％過酸化水素水９ｍｌを滴下した。Example 9 2-(4-cyclohexylphenyl)-propionate 2.61 of 3-methyl-3-(4-cyclohexylphenyl)-pyruvic acid was dissolved in 20 ml of glacial acetic acid and stirred and cooled with 30% filtration. 9 ml of hydrogen oxide water was added dropwise.

室温にもどして５日間攪拌を続けた後、反応液を水中に
注ぎ、エーテル抽出した。After returning to room temperature and continuing stirring for 5 days, the reaction solution was poured into water and extracted with ether.

エーテル層を水洗乾燥後エーテルを減圧留去し、得宴れ
る粗結晶をベンゼン−ヘキサンから再結して２−（４−
シクロへキシルフエニル）−プロピオン酸１．９２ｇを
得た。After washing the ether layer with water and drying, the ether was distilled off under reduced pressure, and the obtained crude crystals were recrystallized from benzene-hexane to give 2-(4-
1.92 g of cyclohexylphenyl)-propionic acid were obtained.

融点１０９．８°〜１１１．３℃、収率８２％（理論値
）。Melting point 109.8°-111.3°C, yield 82% (theoretical value).

元素分析（Ｃ１５Ｈ２０Ｏ２として）結果は次のとおり
である。The elemental analysis (as C15H20O2) results are as follows.

理論値：Ｃ ７７．５５％ Ｈ ８．６８％実測値：Ｃ
７７．４６％ Ｈ ８．７０％実施例 １０ ２−（３−フエノキシフエニル）−プロピオン酸 ３−メチル−３−（３−フエノキシフエニル）−ピルビ
ン酸５．４ｇを酢酸４０ｍｌに溶解させ、攪拌冷却を行
いながら３０％過酸化水素水２０ｍｌを滴下した。Theoretical value: C 77.55% H 8.68% Actual value: C
77.46% H 8.70% Example 10 Dissolve 5.4 g of 3-methyl-3-(3-phenoxyphenyl)-pyruvic acid in 40 ml of acetic acid. Then, 20 ml of 30% hydrogen peroxide solution was added dropwise while stirring and cooling.

室温で１２０時間攪拌した後反応液を低温で半分に濃縮
し、水中に注いで酢酸エチルで抽出した。After stirring at room temperature for 120 hours, the reaction solution was concentrated to half at low temperature, poured into water, and extracted with ethyl acetate.

酢酸エチル層を水洗乾燥した後酢酸エチルを減圧留去し
、無色油状の２−（３−フエノキシフエニル）−プロピ
オン酸３．５０ｇを得た。After the ethyl acetate layer was washed with water and dried, ethyl acetate was distilled off under reduced pressure to obtain 3.50 g of 2-(3-phenoxyphenyl)-propionic acid as a colorless oil.

収率７２％（理論値）。Yield 72% (theoretical value).

元素分析（Ｃ１５Ｈ１４Ｏ３として）結果は次のとおり
である。The elemental analysis (as C15H14O3) results are as follows.

理論値：Ｃ ７４．３６％ Ｈ ５．８３％実測値：Ｃ
７４．５４％ Ｈ ５．９０％実施例 １１ ２−（４−ビフエニリル）−プロピオン酸３−メチル−
３−（４−ビフエニリル）−ピルビン酸２．５４ｇを酢
酸２０ｍｌに溶解させ、攪拌冷却を行いながら３０％過
酸化水素水１０ｍｌを滴下した。Theoretical value: C 74.36% H 5.83% Actual value: C
74.54% H 5.90% Example 11 2-(4-biphenylyl)-3-methyl propionate-
2.54 g of 3-(4-biphenylyl)-pyruvic acid was dissolved in 20 ml of acetic acid, and 10 ml of 30% hydrogen peroxide solution was added dropwise while stirring and cooling.

室温で１２０時間攪拌した後反応液を水中に注ぎ、酢酸
エチルで抽出した。After stirring at room temperature for 120 hours, the reaction solution was poured into water and extracted with ethyl acetate.

酢酸エチル層を水洗し、無水硫酸マグネシウムで乾燥し
た後、酢酸エチルを減圧留去し、得られる粗結晶をベン
ゼンから再結して２−（４−ビフエニリル）−プロピオ
ン酸１．７８ｇを得た。After washing the ethyl acetate layer with water and drying over anhydrous magnesium sulfate, ethyl acetate was distilled off under reduced pressure, and the resulting crude crystals were recrystallized from benzene to obtain 1.78 g of 2-(4-biphenylyl)-propionic acid. .

融点１２２．８°〜１２５℃、収率７８％（理論値）。Melting point 122.8°-125°C, yield 78% (theoretical value).

元素分析（ Ｃ１５Ｈ１４Ｏ２として）結果は次のとお
りである。The elemental analysis (as C15H14O2) results are as follows.

理論値：Ｃ ７９．６２％ Ｈ６．２４％実測値：Ｃ
７９．７８％ Ｈ６．３０％実施例 １２ ２−（４′−フルオロビフエニリル）一プロピオン酸 ３−メチル−３−（４’−フルオロ−４−ビフエニリル
）一ピルビン酸２．７２ｇを酢酸２０ｍｌに溶解させ、
攪拌冷却を行いながら３０％過酸化水素水１０ｍｌを滴
下した。Theoretical value: C 79.62% H6.24% Actual value: C
79.78% H6.30% Example 12 2-(4'-fluorobiphenyl)monopropionic acid 3-methyl-3-(4'-fluoro-4-biphenylyl)monopyruvate 2.72g in acetic acid 20ml Dissolved in
10 ml of 30% hydrogen peroxide solution was added dropwise while stirring and cooling.

室温で１２０時間攪拌した後反応液を水中に注ぎ、酢酸
エチルで抽出した。After stirring at room temperature for 120 hours, the reaction solution was poured into water and extracted with ethyl acetate.

酢酸エチル層を水洗し、無水硫酸マグネシウムで乾燥し
た後酢酸エチルを減圧留去し、得られる粗結晶をベンゼ
ンから再結して２−（４′−フルオロ−４−ビフエニリ
ル）一プロピオン酸１．５６ｇを得た。After washing the ethyl acetate layer with water and drying over anhydrous magnesium sulfate, the ethyl acetate was distilled off under reduced pressure, and the resulting crude crystals were recrystallized from benzene to obtain 2-(4'-fluoro-4-biphenylyl) monopropionic acid 1. 56g was obtained.

融点１３９．８°〜１４０．８℃、収率６４％（理論値
）。Melting point 139.8°-140.8°C, yield 64% (theoretical value).

元素分析（Ｃ１５Ｈ１３ＦＯ２として）結果は次のとお
りである。The elemental analysis (as C15H13FO2) results are as follows.

理論値：Ｃ ７３．７６％ Ｈ５．３６％実測値：Ｃ
７３．６８％ Ｈ５．２９％実施例 １３ ２−（４′−フルオロ−４−ビフエニリル）−プロピオ
ン酸 ３−メチル−３−（４′−フルオロ−４−ビフエニリル
）−ピルビン酸０．３をアセトン３０ｍｌに溶解させ、
はげしく攪拌しながら２４〜３０°で過マンガン酸カリ
ウム０．３ｇを加えた。Theoretical value: C 73.76% H5.36% Actual value: C
73.68% H5.29% Example 13 0.3 of 2-(4'-fluoro-4-biphenylyl)-propionic acid 3-methyl-3-(4'-fluoro-4-biphenylyl)-pyruvic acid in acetone Dissolve in 30ml,
0.3 g of potassium permanganate was added at 24-30° with vigorous stirring.

同温で１０分間そして４０〜４５℃で１０分間攪拌した
のち室温にもどし、４％亜硫酸水素ナトリウム１０ｍｌ
を加え、更に５分間攪拌した。After stirring at the same temperature for 10 minutes and at 40-45℃ for 10 minutes, return to room temperature and add 10 ml of 4% sodium bisulfite.
was added and stirred for an additional 5 minutes.

ついで反応液を濃縮し、残渣を希塩酸で酸性とし、酢酸
エチルで抽出した。The reaction solution was then concentrated, the residue was made acidic with diluted hydrochloric acid, and extracted with ethyl acetate.

酢酸エチル層を水洗したのち無水硫酸マグネシウムで乾
燥し、酢酸エチルを減圧留去して得られる粗結晶をベン
ゼンから再結して２（４′−フルオロ−４−ビフエニリ
ル）−プロピオン酸０．２１ｇを得た。The ethyl acetate layer was washed with water and then dried over anhydrous magnesium sulfate, and the crude crystals obtained by distilling off the ethyl acetate under reduced pressure were recrystallized from benzene to yield 0.21 g of 2(4'-fluoro-4-biphenylyl)-propionic acid. I got it.

融点１３９．４°〜１４０．７℃、収率７８％。Melting point: 139.4° to 140.7°C, yield: 78%.

元素分析（Ｃ１５Ｈ１３ＦＯ２として）結果は次のとお
りである。The elemental analysis (as C15H13FO2) results are as follows.

理論値：Ｃ ７３．７６％ Ｈ５．３６％実測値：Ｃ
７３．５９％ Ｈ５．４９％実施例 １４ ２−（４−シクロへキシルフエニル）−プロピオン酸 ３−メチル−３−（４−シクロへキシルフエニル）−ピ
ルビン酸０．３ｇをアセトン２０ｍｌに溶解させ、はげ
しく攪拌しながら２６〜３０℃で過マンガン酸カリウム
０．２ｇを加えた。Theoretical value: C 73.76% H5.36% Actual value: C
73.59% H5.49% Example 14 0.3 g of 2-(4-cyclohexylphenyl)-propionate 3-methyl-3-(4-cyclohexylphenyl)-pyruvic acid was dissolved in 20 ml of acetone and vigorously dissolved. While stirring, 0.2 g of potassium permanganate was added at 26-30°C.

同温で５分間そして４０〜４５℃で１０分間攪拌した。The mixture was stirred at the same temperature for 5 minutes and then at 40-45°C for 10 minutes.

室温にもどして５％亜硫酸水素ナトリウム１０ｍｌを加
え、室温で５分間攪拌した後反応液を濃縮した。The mixture was returned to room temperature, 10 ml of 5% sodium hydrogen sulfite was added, and after stirring at room temperature for 5 minutes, the reaction solution was concentrated.

残渣に水を加え、希塩酸で酸性とし、エーテル抽出を行
った。Water was added to the residue, acidified with dilute hydrochloric acid, and extracted with ether.

エーテル層を水洗した後無水硫酸マグネシウムで乾燥し
た。The ether layer was washed with water and then dried over anhydrous magnesium sulfate.

エーテルを減圧留去し、得られる粗結晶をヘキサンから
再結して２−（４−シクロへキシルフエニル）−プロピ
オン酸０．２４ｇを得た。The ether was distilled off under reduced pressure, and the resulting crude crystals were recrystallized from hexane to obtain 0.24 g of 2-(4-cyclohexylphenyl)-propionic acid.

融点１１０．０°〜１１１．９℃、収率９０％。元素分
析（Ｃ１５Ｈ２０Ｏ２として）結果は次のとおりである
。Melting point: 110.0° to 111.9°C, yield: 90%. The elemental analysis (as C15H20O2) results are as follows.

理論値：Ｃ７７．５５％ Ｈ８．６８％ 実測値：Ｃ７７．４５％ Ｈ８．６０％ 実施例 １５ ２−（４−第３級プチルフエニル）−プロピオン酸 ３−メチル−３−（４一第３級プチルフエニル）ーピル
ビン酸１．２ｇをアセトン１００ｍｌに溶解させ、はげ
しく攪拌しながら２６〜２８℃で過マンガン酸カリウム
０．８ｇを５分間で加えた。Theoretical value: C77.55% H8.68% Actual value: C77.45% H8.60% Example 15 2-(4-tertiary butylphenyl)-propionate 3-methyl-3-(4-tertiary 1.2 g of (butylphenyl)-pyruvic acid was dissolved in 100 ml of acetone, and 0.8 g of potassium permanganate was added over 5 minutes at 26-28° C. with vigorous stirring.

同温で５分間そして４０〜４５℃で１０分間攪拌した。The mixture was stirred at the same temperature for 5 minutes and then at 40-45°C for 10 minutes.

室温にもどし、５％亜硫酸水素ナトリウム４０ｍｌを加
え、室温で５分間攪拌した後反応液を濃縮した。The temperature was returned to room temperature, 40 ml of 5% sodium hydrogen sulfite was added, and after stirring at room temperature for 5 minutes, the reaction solution was concentrated.

残渣に水を加え、希塩酸で酸性とし、エーテル抽出を行
った。Water was added to the residue, acidified with dilute hydrochloric acid, and extracted with ether.

エーテル層を水洗した後無水硫酸マグネシウムで乾燥し
、エーテルを減圧留去して得られる粗結晶を石油ベンジ
ンから再結して２−（４−第３級プチルフエニル）−プ
ロピオン酸０．９ｇを得た。After washing the ether layer with water, it was dried over anhydrous magnesium sulfate, and the ether was distilled off under reduced pressure. The resulting crude crystals were recrystallized from petroleum benzine to obtain 0.9 g of 2-(4-tertiary butylphenyl)-propionic acid. Ta.

融点１００．６°〜１０２．４℃、収率８５％。Melting point 100.6°-102.4°C, yield 85%.

元素分析（Ｃ１３Ｈ１８Ｏ２として）結果は次のとおり
である。The elemental analysis (as C13H18O2) results are as follows.

理論値：Ｃ ７５．６９％ Ｈ８．８０％実測値：Ｃ
７５．５８％ Ｈ８．７１％実施例 １６ ２−（４−シクロへキシルフエニル）−プロピオン酸 ３−メチル−３−（４−シクロへキシルフエニル）−グ
リシド酸メチル５．８ｇを氷酢酸４０ｍｌに溶解させ、
濃塩酸８ｍｌを加え、１時間還流攪拌した。Theoretical value: C 75.69% H8.80% Actual value: C
75.58% H8.71% Example 16 5.8 g of 3-methyl 2-(4-cyclohexylphenyl)-propionate-3-(4-cyclohexylphenyl)-methyl glycidate was dissolved in 40 ml of glacial acetic acid. ,
8 ml of concentrated hydrochloric acid was added, and the mixture was stirred under reflux for 1 hour.

ついで反応を濃縮し、水を加えてエーテル抽出を行い、
水洗した後濃縮し、残渣４．０ｇをアセトン２００ｍｌ
および水１０ｍｌに溶解させた。Then, the reaction was concentrated, water was added, and ether extraction was performed.
After washing with water, concentrate and add 4.0 g of the residue to 200 ml of acetone.
and dissolved in 10 ml of water.

はげしく攪拌しながら２６〜３０℃で過マンガン酸カリ
２．４ｇを少量ずつ加えた。While stirring vigorously, 2.4 g of potassium permanganate was added little by little at 26-30°C.

同温で５分間、さらに４０〜４５℃で１０分間攪拌した
。The mixture was stirred at the same temperature for 5 minutes and then at 40 to 45°C for 10 minutes.

室温にもどして５％の亜硫酸水素ナトリウム１００ｍｌ
を加え、室温で５分間攪拌した後反応液を濃縮した。Bring to room temperature and add 100ml of 5% sodium bisulfite.
was added, and after stirring at room temperature for 5 minutes, the reaction solution was concentrated.

残渣に希塩酸を加えて酸性とし、エーテル抽出を行った
。Dilute hydrochloric acid was added to the residue to make it acidic, and extraction with ether was performed.

エーテル層を水洗した後無水硫酸マグネシウムで乾燥し
た。The ether layer was washed with water and then dried over anhydrous magnesium sulfate.

エーテルを減圧留去し、得られる粗結晶をヘキサンから
再結して２−（４−シクロへキシルフエニル）プロピオ
ン酸３．０ｇを得た。The ether was distilled off under reduced pressure, and the resulting crude crystals were recrystallized from hexane to obtain 3.0 g of 2-(4-cyclohexylphenyl)propionic acid.

参考例 １ ２−（４−シクロへキシルフエニル）−プロピオンアル
デビドおよび３−メチル−３−（４−シクロへキシルフ
エニル）−ピルビン酸の製造３−メチル−３−（４−シ
クロへキシルフエニル）−グリシド酸メチル５．８ｇを
氷酢酸４０ｍｌに溶解させ、濃塩酸８ｍｌを加え、１時
間攪拌還流を行った。Reference Example 1 Production of 2-(4-cyclohexylphenyl)-propionaldebide and 3-methyl-3-(4-cyclohexylphenyl)-pyruvic acid 3-methyl-3-(4-cyclohexylphenyl)-glyside 5.8 g of methyl acid was dissolved in 40 ml of glacial acetic acid, 8 ml of concentrated hydrochloric acid was added, and the mixture was stirred and refluxed for 1 hour.

ついで反応液を濃縮し、水を加えてエーテル抽出を行い
、水洗した後、炭酸ソーダ水で酸性部を抽出した。The reaction solution was then concentrated, water was added to perform ether extraction, and after washing with water, the acidic portion was extracted with aqueous sodium carbonate.

エーテル層は水洗した後無水硫酸マグネシウムで乾燥し
、エーテルを減圧留去した。The ether layer was washed with water, dried over anhydrous magnesium sulfate, and the ether was distilled off under reduced pressure.

残渣を蒸留して２−（４−シクロへキシルフエニル）−
プロピオンアルデヒド２．９ｇを得た。The residue was distilled to give 2-(4-cyclohexylphenyl)-
2.9 g of propionaldehyde was obtained.

沸点９４°〜９６℃／０．３ｍｍＨｇ、収率６４％。Boiling point 94°-96°C/0.3mmHg, yield 64%.

元素分析（２，４−ジニトロフエニルヒドラゾソＣ２１
Ｈ２４Ｏ４Ｎ４として）結果は次のとおりである。Elemental analysis (2,4-dinitrophenylhydrazoso C21
H24O4N4) The results are as follows.

理論値： Ｃ ６３．６２％ Ｈ ６．１０％ Ｎ １
４．１３％実測値： Ｃ ６３．５０％ Ｈ ５．９５
％ Ｎ １４．０１％一方炭酸ソーダ水抽出部を塩酸で
酸性とし、エーテル抽出を行い、エーテル層る水洗し、
無水硫酸マグネシウムで乾燥した後エーテルを減圧留去
し、得られる粗結晶をベンゼンまたはヘキサンから再結
して３−メチル−３−（４−シクロへキシルフエニル）
−ピルビン酸１．０ｇを得た。Theoretical value: C 63.62% H 6.10% N 1
4.13% actual value: C 63.50% H 5.95
%N 14.01%Meanwhile, the sodium carbonate water extracted portion was made acidic with hydrochloric acid, extracted with ether, and the ether layer was washed with water.
After drying over anhydrous magnesium sulfate, the ether was distilled off under reduced pressure, and the resulting crude crystals were recrystallized from benzene or hexane to give 3-methyl-3-(4-cyclohexyl phenyl).
- 1.0 g of pyruvic acid was obtained.

融点１０１°〜１０２．５℃、収率１７％。Melting point 101°-102.5°C, yield 17%.

元素分析（Ｃ１６ Ｈ２０Ｏ３として）結果は次のとお
りである。The elemental analysis (as C16H20O3) results are as follows.

理論値：Ｃ ７３．８２％ Ｈ ７．７４％実測値：Ｃ
７３．６７％ Ｈ ７．９１％参考例 ２ ２−（３−フエノキシフエニル）−プロピオンアルデヒ
ドおよび３−メチル−３−（３−フエノキシフエニル）
−ピルビン酸の製造 ３−メチル−３−（３−フエノキシフエニル）−グリシ
ド酸イソプロピル１０．３ｇをプロピオン酸１００ｍｌ
に溶解させ、この溶液に５０％硫酸１５ｍｌを加え、１
００℃で１時間攪拌を行った。Theoretical value: C 73.82% H 7.74% Actual value: C
73.67% H 7.91% Reference Example 2 2-(3-phenoxyphenyl)-propionaldehyde and 3-methyl-3-(3-phenoxyphenyl)
-Production of pyruvic acid 10.3 g of isopropyl 3-methyl-3-(3-phenoxyphenyl)-glycidate is added to 100 ml of propionic acid.
Add 15 ml of 50% sulfuric acid to this solution, and add 15 ml of 50% sulfuric acid.
Stirring was performed at 00°C for 1 hour.

ついで反応液を濃縮し、水を加えて酢酸エチルで抽出を
行い、水洗した後、炭酸ソーダ水で酸性物質を抽出した
。Then, the reaction solution was concentrated, water was added, extraction was performed with ethyl acetate, and after washing with water, acidic substances were extracted with sodium carbonate water.

酢酸エチル層を水洗した後無水硫酸マグネシウムで乾燥
し、酢酸エチルを減圧留去し、残渣をシリカゲルカラム
クロマトグラフイーで精製して２−（３−フエノキシフ
エニル）一プロピオンアルデヒド５．１ｇを得た。The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, ethyl acetate was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 5.1 g of 2-(3-phenoxyphenyl)-propionaldehyde. Obtained.

収率６８％。元素分析（Ｃ１５Ｈ１４Ｏ２として）結果
は次のとおりである。Yield 68%. The elemental analysis (as C15H14O2) results are as follows.

理論値：Ｃ ７９．６２％ Ｈ６．２４％実測値：Ｃ
７９．５０％ Ｈ６．０３％一方、炭酸ソーダ水抽出液
を塩酸で酸性とし、酢酸エチル抽出を行い、酢酸エチル
層を水洗し、無水硫酸マグネシウムで乾燥した後酢酸エ
チルを減圧留去して３−メチル−３−（３−フエノキシ
フエニル）−ピルビン酸２．０ｇを得た。Theoretical value: C 79.62% H6.24% Actual value: C
79.50% H6.03% Meanwhile, the aqueous sodium carbonate extract was acidified with hydrochloric acid, extracted with ethyl acetate, the ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, and the ethyl acetate was distilled off under reduced pressure. 2.0 g of -methyl-3-(3-phenoxyphenyl)-pyruvic acid was obtained.

収率２２％。Yield 22%.

元素分析（Ｃ１６Ｈ１４Ｏ４として）結果は次のとおり
である。The elemental analysis (as C16H14O4) results are as follows.

理論値：Ｃ ７１．１０％ Ｈ５．２２％実測値：Ｃ
７１．２９％ Ｈ５．１１％参考例 ３ ２−（４−ビフエニル）−プロピオンアルデヒドおよび
３−メチル−３−（４−ビフエニリル）−ピルビン酸の
製造 ３−メチル−３−（４−ビフエニリル）−グリシド酸エ
チル９．４ｇを酢酸８０ｒｒＬｌに溶解させ、これに濃
塩酸８ＴｒＬｌを加え、１００°Ｃにて７０分間攪拌し
た。Theoretical value: C 71.10% H5.22% Actual value: C
71.29% H5.11% Reference Example 3 Production of 2-(4-biphenyl)-propionaldehyde and 3-methyl-3-(4-biphenylyl)-pyruvic acid 3-methyl-3-(4-biphenylyl)- 9.4 g of ethyl glycidate was dissolved in 80 rrLl of acetic acid, 8TrLl of concentrated hydrochloric acid was added thereto, and the mixture was stirred at 100°C for 70 minutes.

ついで反応液を濃縮し、水を加えて酢酸エチルで抽出し
た。Then, the reaction solution was concentrated, water was added, and the mixture was extracted with ethyl acetate.

酢酸エチル層を水洗した後、炭酸ソーダ水で酸性物質を
抽出した。After washing the ethyl acetate layer with water, acidic substances were extracted with sodium carbonate water.

酢酸エチル層を水洗した後無水硫酸マグネシウムで乾燥
し、ついで酢酸エチルを減圧留去し、得られる粗結晶を
再結して２−（４−ビフエニリル）一 ５８．５℃、収率６０％。The ethyl acetate layer was washed with water and dried over anhydrous magnesium sulfate, and then the ethyl acetate was distilled off under reduced pressure, and the resulting crude crystals were recrystallized to give 2-(4-biphenylyl)-58.5°C, yield 60%.

元素分析（Ｃ１５Ｈ１４０として）結果は次のとおりで
ある。The results of elemental analysis (as C15H140) are as follows.

理論値：Ｃ ８５．６８％ Ｈ ６７１％実測値：Ｃ
８５．５０％ Ｈ６．５４％一方炭酸ソーダ水抽出
液を塩酸で酸性とし、酢酸エチルで抽出を行い、酢酸エ
チル層を水洗し、無水硫酸マグネシウムで乾燥した。Theoretical value: C 85.68% H 671% Actual value: C
85.50% H6.54% On the other hand, the aqueous sodium carbonate extract was acidified with hydrochloric acid, extracted with ethyl acetate, and the ethyl acetate layer was washed with water and dried over anhydrous magnesium sulfate.

酢酸エチルを減圧留去し、得られる粗結晶をベンゼンか
ら再結して３−メチル−３−（４−ビフエニリル）一ピ
ルビン酸１．７１を得た。Ethyl acetate was distilled off under reduced pressure, and the resulting crude crystals were recrystallized from benzene to obtain 1.71 of 3-methyl-3-(4-biphenylyl)monopyruvic acid.

融点１４１．０°〜１４２．２ＱＣ ，収率２０チ。Melting point: 141.0°-142.2QC, yield: 20%.

元素分析（Ｃ１６ＨＬ４０３として）結果は次のとおり
である。The elemental analysis (as C16HL403) results are as follows.

理論値：Ｃ ７５．５７％ Ｈ５．５５％実測値：Ｃ
７５．４９％ Ｈ５．６６％参考例 ４ ２−（４’−−フルオロ−４−ビフエニリル）一プロピ
オンアルデヒドおよび３−メチル−３＝（４′−フルオ
ロー−４−ビフエニリル）一ピルビン酸の製造 ３−メチル−３−（４’−フルオロ−４−ビフエニリル
）一グリシド酸メチル１０．５ｇを氷酢酸１００ｍｌに
溶解させ、この溶液に濃塩酸１０ｍｌを加え、１０００
Ｃにて６０分間攪拌した。Theoretical value: C 75.57% H5.55% Actual value: C
75.49% H5.66% Reference Example 4 Production of 2-(4'--fluoro-4-biphenylyl)-propionaldehyde and 3-methyl-3=(4'-fluoro-4-biphenylyl)-monopyruvate 3 10.5 g of methyl-3-(4'-fluoro-4-biphenylyl) monoglycidate was dissolved in 100 ml of glacial acetic acid, and 10 ml of concentrated hydrochloric acid was added to this solution.
The mixture was stirred at C for 60 minutes.

ついで反応液を濃縮し、水を加えて酢酸エチルで抽出し
た。Then, the reaction solution was concentrated, water was added, and the mixture was extracted with ethyl acetate.

酢酸エチル層を水洗した後、炭酸ソーダ水で酸性物質を
抽出した。After washing the ethyl acetate layer with water, acidic substances were extracted with sodium carbonate water.

酢酸エチル層を水洗Ｉ７た後無水硫酸マグネシウムで乾
燥し、ついで酢酸エチルを減圧留去し、半結晶状の２−
（４′−フルオロ−４−ビフエニリル）一プロピオンア
ルデヒド５，２ｇを得た。The ethyl acetate layer was washed with water, dried over anhydrous magnesium sulfate, and then ethyl acetate was distilled off under reduced pressure to obtain semi-crystalline 2-
5.2 g of (4'-fluoro-4-biphenylyl)-propionaldehyde was obtained.

融点〜４１．４℃、収率６２％。元素分析（２，４−ジ
ニトロフエニルヒドラゾン Ｃ２１Ｈ１７ＦＮ４Ｏ４として）結果は次のとおりであ
る。Melting point ~41.4°C, yield 62%. Elemental analysis (as 2,4-dinitrophenylhydrazone C21H17FN4O4) results are as follows.

理論値：Ｃ ６１．７６％ Ｈ ４．２０％ Ｎ１３．
７２％実測値：Ｃ ６１．５９％ Ｈ ４．１１％ Ｎ
１３．５９％一方炭酸ソーダ水抽出液を塩酸で酸性とし
、酢酸エチルで抽出を行い、酢酸エチル層を水洗し、無
水マグネシウムで乾燥した。Theoretical value: C 61.76% H 4.20% N13.
72% actual value: C 61.59% H 4.11% N
On the other hand, the 13.59% aqueous sodium carbonate extract was made acidic with hydrochloric acid, extracted with ethyl acetate, and the ethyl acetate layer was washed with water and dried over anhydrous magnesium.

酢酸エチルを減圧留去し、得られる粗結晶をベンゼンか
ら再結して３−メチル−３−（４′−フルオロー４−ビ
フエニリル）−ピルビン酸１．５ｇを得た。Ethyl acetate was distilled off under reduced pressure, and the resulting crude crystals were recrystallized from benzene to obtain 1.5 g of 3-methyl-3-(4'-fluoro-4-biphenylyl)-pyruvic acid.

融点１３９．８°〜１４０．８℃、収率１５％。Melting point 139.8°-140.8°C, yield 15%.

元素分析（Ｃ１６Ｈ１３ＦＯ３として）結果は次のとお
りである。The elemental analysis (as C16H13FO3) results are as follows.

Claims (1)

【特許請求の範囲】 １ 一般式 （式中Ｒ１は４一低級アルキルフエニル、４−ビフエニ
リル、４−シクロへキシルフエニル、３−フエノキシフ
エニルまたは４′−フルオロ−４−ビフエニリル基であ
る）の化合物を酸化することを特徴とする、一般式 （式中Ｒ１は前記と同様である）で表わされる２〜（置
換アリール）−プロピオン酸化合物の製法。[Claims] 1 General formula (wherein R1 is 4-lower alkyl phenyl, 4-biphenylyl, 4-cyclohexylphenyl, 3-phenoxyphenyl or 4'-fluoro-4-biphenylyl group) A method for producing a 2-(substituted aryl)-propionic acid compound represented by the general formula (wherein R1 is the same as above), which comprises oxidizing a compound.
JP49086005A 1974-07-29 1974-07-29 Process for producing 2-(substituted aryl)-propionic acid Expired JPS582934B2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP49086005A JPS582934B2 (en) 1974-07-29 1974-07-29 Process for producing 2-(substituted aryl)-propionic acid
DE19752533397 DE2533397A1 (en) 1974-07-29 1975-07-25 PROCESS FOR THE PREPARATION OF 2-ARYLPROPIONIC ACIDS
GB3133775A GB1521906A (en) 1974-07-29 1975-07-25 Process of producing 2-(substituted aryl)-propionic acids

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP49086005A JPS582934B2 (en) 1974-07-29 1974-07-29 Process for producing 2-(substituted aryl)-propionic acid

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP12804777A Division JPS5941976B2 (en) 1977-10-24 1977-10-24 Process for producing 2-(substituted aryl)-propionic acid

Publications (2)

Publication Number Publication Date
JPS5116636A JPS5116636A (en) 1976-02-10
JPS582934B2 true JPS582934B2 (en) 1983-01-19

Family

ID=13874563

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Country Link
JP (1) JPS582934B2 (en)
DE (1) DE2533397A1 (en)
GB (1) GB1521906A (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5535056A (en) * 1978-09-04 1980-03-11 Hamari Yakuhin Kogyo Kk 3-substituted acetophenone and its preparation
JPS5536450A (en) * 1978-09-07 1980-03-14 Hamari Yakuhin Kogyo Kk Preparation of 2-(3-benzoylphenyl)-propionic acid and its intermediate
JPS5538359A (en) * 1978-09-12 1980-03-17 Hamari Yakuhin Kogyo Kk Preparation of 2-(3-benzoylphenyl)-propionic acid
JPS5538360A (en) * 1978-09-12 1980-03-17 Hamari Yakuhin Kogyo Kk Preparation of 2-(3-benzoylphenyl)-propionic acid
DE2950608A1 (en) * 1978-12-29 1980-07-10 Chinoin Gyogyszer Es Vegyeszet METHOD FOR PRODUCING 2- (3-PHENOXY-PHENYL) -PROPIONIC ACID
CA1325222C (en) * 1985-08-23 1993-12-14 Lederle (Japan), Ltd. Process for producing 4-biphenylylacetic acid
US5739352A (en) * 1995-10-19 1998-04-14 United Carbide Chemicals & Plastics Technology Corporation Process for preparing carboxylic acids
US5739385A (en) * 1995-10-19 1998-04-14 Union Carbide Chemicals & Plastics Technology Corporation Process for preparing optically active carboxylic acids
ITMI20012434A1 (en) * 2001-11-20 2003-05-20 Dompe Spa 2-ARYL-PROPIONIC ACIDS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3228831A (en) * 1961-02-02 1966-01-11 Boots Pure Drug Co Ltd Compositions and method for treating symptoms of inflammation, pain and fever

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* Cited by examiner, † Cited by third party
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GB1160725A (en) * 1966-11-25 1969-08-06 Boots Pure Drug Co Ltd Improvements in the Preparation of Phenylalkanoic Acids
GB1382996A (en) * 1971-03-26 1975-02-05 Boots Co Ltd Substituted biphenyls
OA04219A (en) * 1971-12-03 1979-12-31 Rhone Poulenc Sa Novel process for the preparation of (3-benzol-phenyl) -2 propionic acid and the like.
US3927084A (en) * 1973-01-29 1975-12-16 Nisshin Flour Milling Co Process for the production of 2(4-alkylphenyl)propionic acid
JPS5335069B2 (en) * 1973-01-29 1978-09-25

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3228831A (en) * 1961-02-02 1966-01-11 Boots Pure Drug Co Ltd Compositions and method for treating symptoms of inflammation, pain and fever

Also Published As

Publication number Publication date
DE2533397C2 (en) 1990-05-31
DE2533397A1 (en) 1976-02-12
JPS5116636A (en) 1976-02-10
GB1521906A (en) 1978-08-16

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