JPS5817450B2 - Racemization method for optically active α-substituted aryl acetic acid - Google Patents
Racemization method for optically active α-substituted aryl acetic acidInfo
- Publication number
- JPS5817450B2 JPS5817450B2 JP10232578A JP10232578A JPS5817450B2 JP S5817450 B2 JPS5817450 B2 JP S5817450B2 JP 10232578 A JP10232578 A JP 10232578A JP 10232578 A JP10232578 A JP 10232578A JP S5817450 B2 JPS5817450 B2 JP S5817450B2
- Authority
- JP
- Japan
- Prior art keywords
- medoxy
- naphthyl
- propionic acid
- acetic acid
- optically active
- 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
- 238000000034 method Methods 0.000 title description 7
- 230000006340 racemization Effects 0.000 title description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 title 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 10
- 239000002798 polar solvent Substances 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims 1
- 235000019260 propionic acid Nutrition 0.000 claims 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 10
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 description 5
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- XSAYZAUNJMRRIR-UHFFFAOYSA-N 2-acetylnaphthalene Chemical compound C1=CC=CC2=CC(C(=O)C)=CC=C21 XSAYZAUNJMRRIR-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- DKVIPUUJSKIQFZ-UHFFFAOYSA-N 2-naphthalen-2-ylpropanoic acid Chemical compound C1=CC=CC2=CC(C(C(O)=O)C)=CC=C21 DKVIPUUJSKIQFZ-UHFFFAOYSA-N 0.000 description 2
- 241000157855 Cinchona Species 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- FTTATHOUSOIFOQ-UHFFFAOYSA-N 1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine Chemical compound C1NCCN2CCCC21 FTTATHOUSOIFOQ-UHFFFAOYSA-N 0.000 description 1
- QQLIGMASAVJVON-UHFFFAOYSA-N 1-naphthalen-1-ylethanone Chemical compound C1=CC=C2C(C(=O)C)=CC=CC2=C1 QQLIGMASAVJVON-UHFFFAOYSA-N 0.000 description 1
- LUZDYPLAQQGJEA-UHFFFAOYSA-N 2-Methoxynaphthalene Chemical compound C1=CC=CC2=CC(OC)=CC=C21 LUZDYPLAQQGJEA-UHFFFAOYSA-N 0.000 description 1
- DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 0.000 description 1
- 235000021513 Cinchona Nutrition 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- OTGHWLKHGCENJV-UHFFFAOYSA-N glycidic acid Chemical compound OC(=O)C1CO1 OTGHWLKHGCENJV-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- -1 hydroxybutenoic acid ester Chemical class 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- QABLOFMHHSOFRJ-UHFFFAOYSA-N methyl 2-chloroacetate Chemical compound COC(=O)CCl QABLOFMHHSOFRJ-UHFFFAOYSA-N 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
【発明の詳細な説明】
本発明は医薬として有用な光学活性α一置換アリール酢
酸のラセミ化方法に関する。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for racemizing optically active α-monosubstituted arylacetic acids useful as pharmaceuticals.
本発明によれば、ｄ−またはｌ−２−（６−メドキシー
２−ナフチル）−プロピオン酸もしくはそれら両者の混
合物を極性溶媒中で含窒素強塩基で処理することになり
効率的なラセミ化を行なってｄ７−２−（６−メドキシ
ー２−ナフチル）−プロピオン酸を得る新規な方法が提
供される。According to the present invention, efficient racemization is achieved by treating d- or l-2-(6-medoxy-2-naphthyl)-propionic acid or a mixture of both with a strong nitrogen-containing base in a polar solvent. A novel process for obtaining d7-2-(6-medoxy-2-naphthyl)-propionic acid is provided.
従来この化合物のラセミ化方法としては、特公昭４９−
３１９８１号公報に記載されているシンコニジンによる
方法が知られている。Conventionally, as a racemization method for this compound,
A method using cinchonidine described in Japanese Patent No. 31981 is known.
すなわち、ｄ−またはｌ−２−（６−メドキシー２−ナ
フチル）−プロピオン酸をシンコニジンの存在下で極性
溶媒中で１１０〜１２５°Ｃの温度において長時間加熱
してラセミ化を行うものである。That is, racemization is carried out by heating d- or l-2-(6-medoxy-2-naphthyl)-propionic acid in a polar solvent in the presence of cinchonidine at a temperature of 110 to 125 °C for a long period of time. .
しかしながらシンコニン、キニンなどの系統のキナアル
カロイドは異性化しやすり、トキシン類に変換スること
はよく知られている（朝食書店発行「大有機化学複素環
式化合物」第■下巻第１２０〜１２１頁参照）。However, it is well known that cinchona alkaloids such as cinchonine and quinine are isomerized and converted into toxins (see "Large Organic Chemistry Heterocyclic Compounds" published by Shokusen Shoten, Vol. 2, pp. 120-121) ).
従って、特公昭４９−３１９８１号公□報記載のラセミ
化条件においては、シンコニジンが異性化し、そのよう
な異性化生成物が所望の生成物中に混入する可能性があ
るので、好ましい方法とは云えない。Therefore, under the racemization conditions described in Japanese Patent Publication No. 49-31981, cinchonidine may be isomerized and such isomerized products may be mixed into the desired product, so what is the preferred method? I can't say it.
本発明者らは、種々のラセミ化反応条件を検討した結果
、極性溶媒中で従来この種のラセミ化剤としては未知で
あった特殊の含窒素強塩基を使用することによってｄ−
またはｌ−２−（６−メ）・キシ−２−ナフチル）−プ
ロピオン酸のラセミ化が容易に起り、しかも高純度のラ
セメートが得ら□れることを発見し、この発明を完成し
た。As a result of studying various racemization reaction conditions, the present inventors found that d-
Alternatively, the inventors discovered that racemization of l-2-(6-methoxy-2-naphthyl)-propionic acid can easily occur and that a highly pure racemate can be obtained, and have completed this invention.
本発明の反応に用いられる含窒素強塩基は、１．５−ジ
アザビシクロ（５，４，０，ｌウンデセン−５，１，５
−ジアザビシクロ（４，３，０）ノネン−５および１，
４−ジアザビシクロ（２，２，２）オクタンのうちから
選ばれたものである。The nitrogen-containing strong base used in the reaction of the present invention is 1,5-diazabicyclo(5,4,0,l undecene-5,1,5
-diazabicyclo(4,3,0)nonene-5 and 1,
It is selected from 4-diazabicyclo(2,2,2)octane.
使用量は原料１モルに対して１．０〜１．２モルが適当
である。The appropriate amount to be used is 1.0 to 1.2 mol per mol of the raw material.
極性溶媒としてはジオキサン、ジメチルホルムアミド、
ジメチルアセトアミド、ジメチルスルホキシド、ヘキサ
メチルホスホルトリアミド、エチレニングリコール、ピ
リジンなど沸点が１００℃以上のものが挙げられるが、
ジメチルホルムアミドおよびエチレングリコールが工業
上好ましい。Polar solvents include dioxane, dimethylformamide,
Examples include those with a boiling point of 100°C or higher, such as dimethylacetamide, dimethylsulfoxide, hexamethylphosphortriamide, ethylene glycol, and pyridine.
Dimethylformamide and ethylene glycol are commercially preferred.
反応温度は８０℃ないし１８０℃の範囲で可能であるが
、実際上９０℃〜１２０℃の範囲で反応・を行うのが好
ましい。Although the reaction temperature can range from 80°C to 180°C, it is actually preferable to carry out the reaction at a temperature from 90°C to 120°C.
反応時間は反応温度に左右されるが、３時間〜９時間で
反応はほぼ完結する。Although the reaction time depends on the reaction temperature, the reaction is almost completed in 3 to 9 hours.
本発明の原料として用いられるｄ−またはｌ−−２−（
６−メドキシー２−ナフチル）−プロピオン酸はたとえ
ば以下の操作により得られる。d- or l--2-(
6-Medoxy (2-naphthyl)-propionic acid can be obtained, for example, by the following procedure.
２−メトキシナフタレンをニトロベンゼン中塩化アルミ
ニウムの存在下で塩化アセチルで処理して６−メドキシ
ー２−アセチルナフタレンとし、次に６−メドキシー２
−アセチルナフタレンおよびクロル酢酸メチルをカリウ
ム第３級ブチラードの存在下にダルツエン縮合せしめて
３−メチル−３−（６−メドキシー２−ナフチル）−グ
リシド酸エステルを生成させ、ついでグリシド酸エステ
ルを臭化マグネシウムで処理して２−ヒドロキシー：３
−（６−メドキシー２−ナフチル）−３−ブテン酸エス
テルとし、次にヒドロキシブテン酸エステルをメタノー
ル中ナトリウムメチラートで処理した後加水分解を行い
、次に過酸化水素で酸化してｄｌ−２−（６−メドキシ
ー２−ナフチル）−プロピオン酸を生成させる。2-Methoxynaphthalene is treated with acetyl chloride in the presence of aluminum chloride in nitrobenzene to give 6-medoxy 2-acetylnaphthalene, then to give 6-medoxy 2-acetylnaphthalene.
- Dartzene condensation of acetylnaphthalene and methyl chloroacetate in the presence of potassium tert-butyralate to form 3-methyl-3-(6-medoxy-2-naphthyl)-glycidate, followed by bromination of the glycidate. Treated with magnesium to 2-hydroxy:3
-(6-Medoxy-2-naphthyl)-3-butenoic acid ester, then the hydroxybutenoic acid ester was treated with sodium methylate in methanol followed by hydrolysis, and then oxidized with hydrogen peroxide to give dl-2. -(6-medoxy-2-naphthyl)-propionic acid is produced.
このｄｌ−酸をメタノール中でシンコニジンで処理する
と、析出結晶は右旋性を示し、他方ろ液からは左旋性を
示す結晶が得られる。When this dl-acid is treated with cinchonidine in methanol, the precipitated crystals exhibit dextrorotatory properties, while the filtrate yields levorotatory crystals.
これらの反応を式を以て示せば、次のとおりである。The formulas for these reactions are as follows.
次に実施例を挙げて説明する。Next, an example will be given and explained.
ただし本発明はこれらの実施例により限定されるもので
はない。However, the present invention is not limited to these Examples.
実施例 １ ５ 〔α〕。Example 1 5 [α].
−−４２，８° （１デクロロホルム）の２−（６−メ
ドキシー２−ナフチル）−プロピオン酸（ｌ一体８４．
２％およびｄ一体１５．８％の混合物）６．９ｇをジメ
チルホルムアミド３０ｍ１に溶解させ、１，５−ジアザ
ビシクロ（５，４，０）ウンデセン−５（！１１１）を
加え、１１０°〜１１５°Ｃで４時間加熱した。--42,8° (1 dechloroform) of 2-(6-medoxy-2-naphthyl)-propionic acid (l 84.
Dissolve 6.9 g of a mixture of 2% and 15.8% of d in 30 ml of dimethylformamide, add 1,5-diazabicyclo(5,4,0) undecene-5 (!111), and mix at 110° to 115°. The mixture was heated at C for 4 hours.
希塩酸で酸性化した後、酢酸エチルで抽出した。After acidifying with dilute hydrochloric acid, 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、そして無水硫
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.
酢酸エチルを減圧下に留去してｄｌ−，２−（６−メド
キシー２−ナフチル）−プロピオン酸６．２５
９ヲ４ｆｔ。Ethyl acetate was distilled off under reduced pressure to give 6.25 9.4 ft of dl-,2-(6-medoxy-2-naphthyl)-propionic acid.
〔α〕 −０° （１％クロロホルム）っ実施例 ２
５
〔α）＝−４２，８（１係クロロホルム）の２一（６−
メドキシー２−ナフチル）−プロピオン酸（ｌ一体８４
．２係およびｄ一体１５．８％の混合物）６．９ｇをジ
オキサン１００Ｔｔｌに溶解させ、そして１，５−ジア
ザビシクロ（５，４，０）ウンデセン−５（４，ｌＩ）
を加えて９時間還流した。[α] −0° (1% chloroform) Example 2 5 [α) = −42,8 (1% chloroform) 21 (6−
Medoxy-2-naphthyl)-propionic acid (1 unit 84
．． 6.9 g of 15.8% mixture of 2 and d monomers) were dissolved in 100 Ttl of dioxane and 1,5-diazabicyclo(5,4,0) undecene-5(4,lI)
was added and refluxed for 9 hours.
反応液を濃縮し、残渣に希塩酸を加えそして酢酸エチル
で抽出した。The reaction solution was concentrated, diluted hydrochloric acid was added to the residue, 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そして無水硫酸
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.
酢酸エチルを減圧下に留去してｄｉ−２−（６−メドキ
シー２−ナフチル）−プロピオン酸６．３９を得２５
た。Ethyl acetate was distilled off under reduced pressure to obtain 6.39 g of di-2-(6-medoxy-2-naphthyl)-propionic acid.
〔α〕 −０° （１％クロロホルム）。実施例 ３
５
〔α〕 ミ＋５４．０° （１％クロロホルム）の２−
（６−メドキシー２−ナフチル）−プロピオン酸（ｄ−
一体３．２係およびｌ−一体、８係の混合物）６．９ｇ
をジメチルスルホキシド３０ｍ１に溶解させ、そして１
，５−ジアザビシクロ（４，３，０）ノネン−５（３，
８ｇ ）を加えて１１ｏ〜１１５℃で５時間加熱攪拌を
行った。[α] −0° (1% chloroform). Example 3 5 [α] 2- of Mi+54.0° (1% chloroform)
(6-medoxy-2-naphthyl)-propionic acid (d-
6.9 g
was dissolved in 30 ml of dimethyl sulfoxide, and 1
,5-diazabicyclo(4,3,0)nonene-5(3,
8g) was added thereto and heated and stirred at 11°C to 115°C for 5 hours.
ついで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 then 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.
酢酸エチルを減圧留去してｄｉ−２＝（６−メドキシー
２−ナフチル）−プロピオン５
酸６．２ｇを得た。Ethyl acetate was distilled off under reduced pressure to obtain 6.2 g of di-2=(6-medoxy-2-naphthyl)-propionic penta-acid.
〔α）＝ｏ”（ｉ％クロロポルム）。[α)=o” (i% chloroporum).
実施例 ４
５
〔α） ＝＋５４．Ｏ° （１％クロロホルム）の２
−（６−メドキシー２−す７チル）−プロピオン酸（ｄ
−一体３．２％およびｌ−一体、８％の混合物）６．’
ｌをエチレングリコール５０ｍ１に溶解させそして１，
４−ジアザビシクロ（２，２，２、！−Ａ’；’タン（
３，４，！ｉ’）を加えて１１５〜１２０℃で７時間加
熱および攪拌を行った。Example 4 5 [α) = +54. 2 of O° (1% chloroform)
-(6-medoxy-2-su7tyl)-propionic acid (d
- a mixture of 3.2% and l - 8%) 6. '
1 in 50 ml of ethylene glycol and 1,
4-diazabicyclo(2,2,2,!-A';'tan(
3, 4,! i') was added and heated and stirred at 115-120°C for 7 hours.
反応液を濃縮した後希塩酸を加えて酸性化し、酢酸エチ
ルで抽出した。After the reaction solution was concentrated, it was acidified by adding 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.
酢酸エチルを減圧下に留去してｄｌ−２−（６−メドキ
シー２−ナフチル）５
一プロピオン酸６．３ｇを得た。Ethyl acetate was distilled off under reduced pressure to obtain 6.3 g of dl-2-(6-medoxy-2-naphthyl)5 monopropionic acid.
〔α〕 ＝０゜（１係クロロホルム）。[α] = 0° (1st unit chloroform).
９実施例 ５
５
〔α〕 ＝６３．５° （ｌ係りロロホルム）の２〜（
６−メドキシー２−ナフチル）−プロピオン酸１ 一体
１００％ ）６．９ｇをジメチルホルムアクミド３０Ｔ
Ｉｌｌに溶解させ、ｉ、５−ジアザビシクロ（５，４，
０）ウンデセン−５（５ｇ）を加え、１１０°〜１１５
℃で４時間加熱した。9 Example 5 5 [α] = 63.5° (L-related loloform) 2~(
6-Medoxy (2-naphthyl)-propionic acid 1 (100%) 6.9g was dissolved in dimethylformacamide 30T.
i,5-diazabicyclo(5,4,
0) Add undecene-5 (5g) and heat from 110° to 115°
Heated at ℃ for 4 hours.
希塩酸で酸性化した後、酢酸エチルで抽出した。After acidifying with dilute hydrochloric acid, 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、そして無水硫
酸フ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.
酢酸エチルを減圧下に留去してｄｌ−１−（６−メドキ
シー２−ナフチル）５
一プロピオン酸６．２９ ヲ’４ｊ＝。Ethyl acetate was distilled off under reduced pressure to give dl-1-(6-medoxy-2-naphthyl)5 monopropionic acid 6.29 o'4j=.
〔α〕 ＝０゜（１係クロロホルム）。[α] = 0° (1st unit chloroform).
Claims (1)
）プロピオン酸もしくはそれら両者の混合物を極性溶媒
中で１，５−ジアザビシクロ（５，４゜０〕ウンデセン
−５，１，５−ジアザビシクロ［４，３，０）ノネン−
５および１．１−ジアザビシクロ（２，２，２）オクタ
ンからなる群から選ばれた含窒素強塩基で処理すること
を特徴とするｄＡ −２−（６−メドキシー２−ナフチ
ル）−プロピオン酸の製法。1 d- or 7-2-(6-medoxy-2-naphthyl)propionic acid or a mixture of both in a polar solvent in a polar solvent. 4,3,0) Nonene-
of dA-2-(6-medoxy-2-naphthyl)-propionic acid, which is treated with a strong nitrogen-containing base selected from the group consisting of 5- and 1.1-diazabicyclo(2,2,2)octane. Manufacturing method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10232578A JPS5817450B2 (en) | 1978-08-24 | 1978-08-24 | Racemization method for optically active α-substituted aryl acetic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10232578A JPS5817450B2 (en) | 1978-08-24 | 1978-08-24 | Racemization method for optically active α-substituted aryl acetic acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5528952A JPS5528952A (en) | 1980-02-29 |
| JPS5817450B2 true JPS5817450B2 (en) | 1983-04-07 |
Family
ID=14324392
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10232578A Expired JPS5817450B2 (en) | 1978-08-24 | 1978-08-24 | Racemization method for optically active α-substituted aryl acetic acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5817450B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02292235A (en) * | 1989-05-08 | 1990-12-03 | Sumitomo Chem Co Ltd | Racemization of optically active alpha-isopropyl-p-chlorophenylacetic acid or its diastereoisomer salt |
-
1978
- 1978-08-24 JP JP10232578A patent/JPS5817450B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| JPS5528952A (en) | 1980-02-29 |
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