JPH0428268B2 - - Google Patents
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- Publication number
- JPH0428268B2 JPH0428268B2 JP59267434A JP26743484A JPH0428268B2 JP H0428268 B2 JPH0428268 B2 JP H0428268B2 JP 59267434 A JP59267434 A JP 59267434A JP 26743484 A JP26743484 A JP 26743484A JP H0428268 B2 JPH0428268 B2 JP H0428268B2
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- Prior art keywords
- epoxy
- methoxyphenyl
- salt
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- formula
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Description
【発明の詳細な説明】
本発明は光学活性なエポキシプロピオン酸エス
テル誘導体に関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to optically active epoxypropionate derivatives.
さらに詳しくは、医薬として有用な冠血管拡張
剤・塩酸ジルチアゼムの中間原料として重要な一
般式
（式中Ｒは炭素数１〜４個の低級アルキル基を示
す）で表わされる新規（−）−（2R*、3S*）−２、
３−エポキシ−３−（４−メトキシフエニル）プ
ロピニオン酸エステルの製造法に関する。 More specifically, the general formula is important as an intermediate raw material for diltiazem hydrochloride, a coronary vasodilator that is useful as a pharmaceutical. (In the formula, R represents a lower alkyl group having 1 to 4 carbon atoms) Novel (-)-(2R * , 3S * )-2,
The present invention relates to a method for producing 3-epoxy-3-(4-methoxyphenyl)propinionic acid ester.
下式で示される化合物
は分子内に２つの不斉炭素を有することから理論
的には４種類の光学異性体が存在する。これらの
うち、（＋）−（2S、3S）体のみが強力な薬効を有
し、塩酸ジルチアゼムとして知られている。この
ため塩酸ジルチアゼムを合成するにあたつては欲
する光学異性体に誘導する方法、例えば光学分割
の操作が必要となる。従来、中間体の光学分割は
種々行なわれており、例えば特公昭53−18038、
特開昭57−136581、および特開昭58−32872に記
載されている。これらの方法はその工程途中、あ
るいは最終工程において光学分解がなされてい
る。光学分割という方法を用いる製造法では、一
方の鏡像体が不必要な場合、ラセミ化等で回収が
できないときは、少なくとも半量が無駄になるた
め、不斉炭素が生ずる早期の段階で光学活性体を
用いた方が有利である。 Compound represented by the following formula Because it has two asymmetric carbon atoms in its molecule, there are theoretically four types of optical isomers. Of these, only the (+)-(2S,3S) form has strong medicinal efficacy and is known as diltiazem hydrochloride. Therefore, in synthesizing diltiazem hydrochloride, a method of inducing the desired optical isomer, such as optical resolution, is required. Conventionally, optical resolution of intermediates has been carried out in various ways.
It is described in JP-A-57-136581 and JP-A-58-32872. In these methods, optical decomposition is performed during the process or in the final process. In production methods that use optical resolution, if one enantiomer is unnecessary or cannot be recovered due to racemization, at least half of the enantiomer is wasted, so the optically active form is removed at an early stage when asymmetric carbon is generated. It is more advantageous to use
しかしながら、塩酸ジルチアゼム合成の出発原
料と考えられる光学活性な（2R*、3S*）−２、３
−エポキシ−３−（４−メトキシフエニル）プロ
ピオン酸類の合成法は、これまでに報告されたこ
とはない。 However, optically active (2R * , 3S * )-2,3, which is considered to be the starting material for the synthesis of diltiazem hydrochloride,
A method for synthesizing -epoxy-3-(4-methoxyphenyl)propionic acids has never been reported.
また、出発原料としての光学活性な遊離の
（−）−（2R*、3S*）−２、３−エポキシ−３−（４
−メトキシフエニル）プロピオン酸はそのラセミ
体と同様不安定な化合物と考えられるため、これ
を単離して取扱うことは非常に困難である。 In addition, optically active free (-)-(2R * , 3S * )-2,3-epoxy-3-(4
-Methoxyphenyl)propionic acid is considered to be an unstable compound like its racemate, so it is very difficult to isolate and handle it.
以上の観点から、安定な光学活性（−）−
（2R*、3S*）−２、３−エポキシ−３−（４−メト
キシフエニル）プロピオン酸類を得ることは新規
で有用なことと考える。 From the above viewpoint, stable optical activity (-)-
We believe that it is novel and useful to obtain (2R * , 3S * )-2,3-epoxy-3-(4-methoxyphenyl)propionic acids.
本発明者は、鋭意検討の結果、不安定な遊離の
（−）−（2R*、3S*）−２、３−エポキシ−３−（４
−メトキシフエニル）プロピオン酸を経由するこ
となく一般式
（式中Aは有機塩基の共役酸またはアルカリ金
属イオンを示す）
で表わされる（−）−（2R*、3S*）−２、３−エポ
キシ−３−（４−メトキシフエニル）プロピオン
酸塩をR2SO4（式中Ｒは炭素数１〜４個の低級ア
ルキル基を示す）、又は１−メチル−２−ハロピ
リジニウム塩の存在下にROH（式中Ｒは前記と同
じ）を作用させることによりエステル化すること
により本発明化合物である一般式
（式中Ｒは前記と同じ）で表わされる（−）−
（2R*、3S*）−２、３−エポキシ−３−（４−メト
キシフエニル）プロピオン酸エステルを高収率で
得ることに成功した。 As a result of extensive studies, the present inventor discovered that unstable free (-)-(2R * , 3S * )-2,3-epoxy-3-(4
-methoxyphenyl)propionic acid without going through the general formula (-)-(2R * ,3S * )-2,3-epoxy-3-(4-methoxyphenyl)propionate represented by (in the formula, A represents the conjugate acid of the organic base or an alkali metal ion) R 2 SO 4 (in the formula, R represents a lower alkyl group having 1 to 4 carbon atoms) or ROH (in the formula, R is the same as above) in the presence of a 1-methyl-2-halopyridinium salt. The compound of the present invention is esterified by (-)- (in the formula, R is the same as above)
(2R * ,3S * )-2,3-epoxy-3-(4-methoxyphenyl)propionic acid ester was successfully obtained in high yield.
以上の通り本発明者らは塩酸ジルチアゼムを得
るための新規で重要な出発原料を、全く新しく独
創的な、しかも工業的に有利な製造法で見出し、
本発明を完成するに至つた。 As described above, the present inventors discovered a new and important starting material for obtaining diltiazem hydrochloride using a completely new and original production method that is also industrially advantageous.
The present invention has now been completed.
本発明をさらに詳細に説明する。 The present invention will be explained in further detail.
原料となる化合物（）は本件と同一出願人の
同日付特許出願に係る発明の名称「新規な光学活
性エポキシプロピオン酸誘導体およびその製造
法」に従つて製造される。次いで得られた化合物
（）をR2SO4（式中Ｒは前記と同じ）、又は１−
メチル−２−ハロピリジニウム塩の存在下に
ROH（式中Ｒは前記と同じ）を作用させることに
よりエステル化し、光学活性（2R*、3S*）−２、
３−エポキシ−３−（４−メトキシフエニル）プ
ロピオン酸エステル（）とする。例えばメチル
エステルを得る反応では、ジメチルホルムアミド
溶媒中、炭酸水素ナトリウムを加えて、硝酸ジメ
チルと化合物（）を数時間反応させればよい。
あるいは化合物（）に対して１−メチル−２−
クロロピリジニウム・メチル硫酸塩、トリエチル
アミン、メタノールを等モル量用い、ジクロロメ
タン中で反応させても良い。 The raw material compound () is produced according to the title of the invention titled "Novel optically active epoxypropionic acid derivative and its production method" related to a patent application filed on the same date by the same applicant as the present case. Then, the obtained compound () is converted into R 2 SO 4 (wherein R is the same as above), or 1-
In the presence of methyl-2-halopyridinium salt
Esterified by the action of ROH (in the formula, R is the same as above), optically active (2R * , 3S * )-2,
3-epoxy-3-(4-methoxyphenyl)propionic acid ester (). For example, in a reaction to obtain a methyl ester, dimethyl nitrate and compound () may be reacted for several hours in a dimethylformamide solvent by adding sodium hydrogen carbonate.
Or 1-methyl-2- for compound ()
The reaction may be carried out in dichloromethane using equimolar amounts of chloropyridinium methyl sulfate, triethylamine, and methanol.
なお、本発明化合物（）は下式の通りを経
由して塩酸ジルチアゼル合成における公知の重要
中間体（＋）−（2S、3S）−３−（２−アミノフエ
ニルチオ）−２−ヒドロキシ−３−（４−メトキシ
フエニル）プロピオン酸（）へと誘導できた。 The compound of the present invention () is a known important intermediate (+)-(2S,3S)-3-(2-aminophenylthio)-2-hydroxy- in the synthesis of dilthiazole hydrochloride via the following formula. It was possible to derive 3-(4-methoxyphenyl)propionic acid ().
参考例 １
アセトニトリル108mlおよび水12mlの混合溶媒
によく粉砕した（±）−（2RS、3SR）−２、３−
エポキシ−３−（４−メトキシフエニル）プロピ
オン酸カリウム塩11.61ｇ（50.0mmol）および
（−）−（Ｓ）−α−メチルベンジルアミン・1/2硫
酸塩8.51ｇ（50.0mmol）を加え室温にて30分間
はげしく撹拌する。不溶物を別し液を−20℃
にて２時間冷却すると無色針状晶が析出するので
これを過し、（−）−２（2R*、3S*）−２、３−
エポキシ−３−（４−メトキシフエニル）プロピ
オン酸・（−）−（Ｓ）−α−メチルベンジルアミン
塩〔以後（−）−１〜・（−）−２〜塩と略記する〕
5.60ｇを得た。収率〔全塩の半量を100％として
計算、以下同じ〕71.0％。mp127.5−128.5℃
（分解）〔α〕23 D−120°（c1.02、メタノール）
また、先に別した不溶物をメタノールより洗
浄し洗浄液を減圧下濃縮乾固して得られる固体を
アセトニトリルより洗浄して（−）−１〜・（−）−
２〜塩〕0.60ｇ（7.6ｇ）を得た。この塩は上記塩
とIRが一致した。mp126.5−127℃
（分解）〔α〕23 D−117°（c1.07、メタノール）
IR（KBr）cm-1；3440、3000〜2950、2700、
2520、2200、1630、1610、1565、1535、1510、
1410、1290、1250、880、765、700
1HNMR（CDCl3／CD3OD＝6/1）δ；1.62（ｄ、
3H、Ｊ＝７Hz、−CHCＨ＝3）
3.35（ｄ、1H、Ｊ＝２Hz、エポキシ環プロト
ン）
3.73（ｄ、1H、Ｊ＝２Hz、エポキシ環プロト
ン）
3.80（ｓ、3H、−OCＨ＝3）
4.36（ｑ、1H、Ｊ＝７Hz、−ＣＨ＝CH3）
6.8−7.2（ｍ、4H、芳香族プロトン）
7.2−7.5（ｍ、5H、芳香族プロトン）
参考例 ２
（−）−１〜・（−）−２〜塩4.41ｇ（14.0mmol）を
乾燥ベンゼン14mlに懸濁させこれに室温で、95％
ナトリウムメトキシド0.80ｇの乾燥メタノール溶
液（14ml）を徐々に加える。室温で１時間撹拌
後、反応液を過しベンゼンで洗浄して（−）−
２（2R*、3S*）−２、３−エポキシ−３−（４−メ
トキシフエニル）プロピオン酸ナトリウム塩2.68
ｇを得た。収率88.4％、mp約220℃
（分解）〔α〕23 D−158°（c0.697、アセトン：水＝
1.0：1.0）
IR（KBr）cm-1；3040、3005〜2950、2900、
2835、1605、1510、1435、1415、1245、1020、
890、830
1HNMR（（CD3）2CO：D2O＝１：１；内部標準
DSS）δ；3.47（ｄ、1H、Ｊ＝２Hz、エポキシ環
プロトン）
3.83（ｓ、3H、−OCＨ＝3）
3.95（ｄ、1H、Ｊ＝２Hz、エポキシ環プロト
ン）
6.96（ｄ、2H、Ｊ＝8.6Hz、芳香族プロトン）
7.31（ｄ、2H、Ｊ＝8.6Hz、芳香族プロトン）
参考例 ３
２−クロロピリジン11.36ｇ（100.0mmol）に
乾燥ジクロロエタン15mlを加え、加熱還流下ジメ
チル硫酸12.61ｇ（100.0mmol）のジクロロエタ
ン15ml溶液を滴下する。１時間加熱還流後室温ま
で冷却して１−メチル−２−クロロピリジニウム
メチル硫酸塩溶液を得た。これをメスフラスコに
移しジクロロメタンを用いて正確に100mlとした。
さらに精製することなく、これを以下の実施例に
用いた。 Reference example 1 (±)-(2RS, 3SR)-2, 3- well ground in a mixed solvent of 108 ml of acetonitrile and 12 ml of water
Add 11.61 g (50.0 mmol) of epoxy-3-(4-methoxyphenyl)propionate potassium salt and 8.51 g (50.0 mmol) of (-)-(S)-α-methylbenzylamine 1/2 sulfate to room temperature. Stir vigorously for 30 minutes. Separate the insoluble matter and cool the liquid to -20℃
When cooled for 2 hours, colorless needle-like crystals precipitate, which is filtered out and (-)-2 (2R * , 3S * )-2, 3-
Epoxy-3-(4-methoxyphenyl)propionic acid/(-)-(S)-α-methylbenzylamine salt [hereinafter abbreviated as (-)-1~/(-)-2~ salt]
Obtained 5.60g. Yield [calculated with half of the total salt as 100%, the same applies hereinafter] 71.0%. mp127.5−128.5℃ (decomposition) [α] 23 D −120° (c1.02, methanol) In addition, the previously separated insoluble matter was washed with methanol, and the washing liquid was concentrated to dryness under reduced pressure. After washing with acetonitrile, (-)-1~・(-)-
2~Salt] 0.60g (7.6g) was obtained. The IR of this salt matched that of the above salt. mp126.5−127℃ (decomposition) [α] 23 D −117° (c1.07, methanol) IR (KBr) cm -1 ; 3440, 3000~2950, 2700,
2520, 2200, 1630, 1610, 1565, 1535, 1510,
1410, 1290, 1250, 880, 765, 700 1 HNMR (CDCl 3 /CD 3 OD=6/1) δ; 1.62 (d,
3H, J = 7Hz, -CHCH = 3 ) 3.35 (d, 1H, J = 2Hz, epoxy ring proton) 3.73 (d, 1H, J = 2Hz, epoxy ring proton) 3.80 (s, 3H, -OCH = 3 ) 4.36 (q, 1H, J=7Hz, -CH=CH 3 ) 6.8-7.2 (m, 4H, aromatic proton) 7.2-7.5 (m, 5H, aromatic proton) Reference example 2 (-)-1~・(-)-2 ~ Suspend 4.41 g (14.0 mmol) of salt in 14 ml of dry benzene and add to this at room temperature, 95%
A solution of 0.80 g of sodium methoxide in dry methanol (14 ml) is slowly added. After stirring at room temperature for 1 hour, the reaction solution was filtered and washed with benzene to give (-)-
2(2R * ,3S * )-2,3-epoxy-3-(4-methoxyphenyl)propionate sodium salt 2.68
I got g. Yield 88.4%, mp approx. 220℃ (decomposition) [α] 23 D −158° (c0.697, acetone:water =
1.0:1.0) IR (KBr) cm -1 ; 3040, 3005~2950, 2900,
2835, 1605, 1510, 1435, 1415, 1245, 1020,
890, 830 1 HNMR ((CD 3 ) 2 CO:D 2 O=1:1; Internal standard
DSS) δ; 3.47 (d, 1H, J = 2Hz, epoxy ring proton) 3.83 (s, 3H, -OCH = 3 ) 3.95 (d, 1H, J = 2Hz, epoxy ring proton) 6.96 (d, 2H, J = 8.6 Hz, aromatic proton) 7.31 (d, 2H, J = 8.6 Hz, aromatic proton) Reference example 3 15 ml of dry dichloroethane was added to 11.36 g (100.0 mmol) of 2-chloropyridine, and 12.61 g of dimethyl sulfate was added under heating under reflux. (100.0 mmol) in 15 ml of dichloroethane is added dropwise. After heating under reflux for 1 hour, the mixture was cooled to room temperature to obtain a 1-methyl-2-chloropyridinium methyl sulfate solution. This was transferred to a volumetric flask and dichloromethane was used to make exactly 100 ml.
This was used in the following examples without further purification.
実施例 １
（−）−（2R*、3S*）−２、３−エポキシ−３−
（４−メトキシフエニル）プロピオン酸ナトリウ
ム塩〔以後（−）−３〜と略記する〕259ｇ
（12.0mmol）を塩化メチレン12mlに懸濁させ、ト
リメチルアミン1.34ｇ（13.2mmol）およびメタ
ノール−塩化メチレン溶液（メタノールmmol／
ml含有）13.2mlを加えよく撹拌する。これに室温
で参考例３で得た１−メチル−２−クロロピリジ
ニウムメチル硫酸塩溶液13.2ml（13.3mmol）を
徐々に加える。反応液を室温で一液撹拌後、溶媒
を減圧下留去し、新たに酢酸エチルを加え、水お
よび飽和食塩水で洗浄する。芒硝で乾燥後溶媒を
留去し、残渣を蒸溜し（−）−（2R*、3S*）−２、
３−エポキシ−３−（４−メトキシフエニル）プ
ロピオン酸メチルエステル2.08ｇを得た。収率
83.2％bp99−101℃／2.5×10-2Torr〔α〕23 D−160°
（c0.892、クロロホルム）
IR（neat）cm-1；3020、2960、2920、2840、
1760、1615、1515、1440、1250、1030、835
1HNMR（CDCl3）δ；3.50（ｄ、1H、Ｊ＝２
Hz、エポキシ環プロトン）
3.80and3.81（Ｓ×２、6H、−OCＨ３−and−
CO2CＨ３−）
4.04（ｄ、1H、Ｊ＝２Hz、エポキシ環プロト
ン）
6.86（ｄ、2H、Ｊ＝8.8Hz、芳香族プロトン）
7.19（ｄ、2H、Ｊ＝8.8Hz、芳香族プロトン）
実施例 ２
（−）−３〜4.32ｇ（20.0mmol）にジメチルホル
ムアミド20mlおよび粉末状の炭酸水素ナトリウム
6.72ｇ（80.0mmol）を加え撹拌する。これにジ
メチル硫酸5.04ｇ（40.0mmol）を加える。16時
間後、反応混合物を氷水200mlに注入しエーテル
で抽出後水で洗浄する。エーテル層を芒硝で乾燥
し溶媒を留去後（−）−（2R*、3S*）−２、３−エ
ポキシ−３−（４−メトキシフエニル）プロピオ
ン酸メチルエステル2.45ｇを得た。収率58.9％
IR、1HNMRの機器データは実施例１のそれと完
全に一致した。〔α〕23 D−155°（c0.897、クロロホル
ム）bp 107〜113℃／0.12Torr
実施例 ３
（−）−３〜3.389ｇ（18.0mmol）を塩化メチレ
ン30mlに懸濁させ、トリエチルアミン2.00ｇ
（19.8mmol）およびエタノール0.91ｇ
（19.8mmol）をすばやく加え、よく撹拌する。こ
れに室温で参考例３で得た１−メチル−２−クロ
ロピリジニウムメチル硫酸塩溶液19.8ml
（19.8mmol）を徐々に加える。反応液を室温で一
夜撹拌後、溶媒を減圧下留去し、新たに酢酸エチ
ルを加え、酢酸エチル層を水続いて飽和食塩水で
洗浄する。芒硝にて乾燥後、溶媒を留去し、残渣
を蒸留して、（−）−（2R*、3S*）−２、３−エポ
キシ−３−（４−メトキシフエニル）プロピオン
酸エチルエステル3.33ｇを得た。収率83.3ｇ
bp110−111℃／2.5×10-2Torr〔α〕23 D−152°
（c1.10、クロロホルム）
IR（neat）cm-1；2990、2950、2910、2840、
1760、1615、1515、1440、1300、1250、1200、
1175、1030、835、780
1HNMR（CDCl3）δ；1.32（ｔ、3H、Ｊ＝７
Hz、−OCH2CＨ３＝
3.48（ｄ、1H、Ｊ＝２Hz、エポキシ環プロト
ン）
3.80（ｓ、3H、−OCＨ３＝）
4.03（ｄ、1H、Ｊ＝２Hz、エポキシ環プロト
ン）
4.27（ｑ、2H、Ｊ＝７Hz、−OCＨ２＝CH3
6.87（ｄ、2H、Ｊ＝8.8Hz、芳香族プロトン）
7.21（ｄ、2H、Ｊ＝8.8Hz、芳香族プロトン）Example 1 (-)-(2R * , 3S * )-2,3-epoxy-3-
(4-methoxyphenyl)propionate sodium salt [hereinafter abbreviated as (-)-3~] 259g
(12.0 mmol) was suspended in 12 ml of methylene chloride, 1.34 g (13.2 mmol) of trimethylamine and a methanol-methylene chloride solution (mmol/mmol of methanol/
ml) Add 13.2ml and stir well. To this was gradually added 13.2 ml (13.3 mmol) of the 1-methyl-2-chloropyridinium methyl sulfate solution obtained in Reference Example 3 at room temperature. After stirring the reaction solution at room temperature, the solvent is distilled off under reduced pressure, ethyl acetate is added again, and the mixture is washed with water and saturated brine. After drying with Glauber's salt, the solvent was distilled off and the residue was distilled (-)-(2R * , 3S * )-2,
2.08 g of 3-epoxy-3-(4-methoxyphenyl)propionic acid methyl ester was obtained. yield
83.2%bp99−101℃／2.5×10 -2 Torr〔α〕 23 D −160°
(c0.892, chloroform) IR (neat) cm -1 ; 3020, 2960, 2920, 2840,
1760, 1615, 1515, 1440, 1250, 1030, 835 1 HNMR (CDCl 3 ) δ; 3.50 (d, 1H, J = 2
Hz, epoxy ring proton) 3.80and3.81 (S×2, 6H, -OCH3 -and-
CO 2 CH 3 −) 4.04 (d, 1H, J = 2Hz, epoxy ring proton) 6.86 (d, 2H, J = 8.8Hz, aromatic proton) 7.19 (d, 2H, J = 8.8Hz, aromatic proton) Example 2 20 ml of dimethylformamide and powdered sodium hydrogen carbonate to (-)-3 to 4.32 g (20.0 mmol)
Add 6.72g (80.0mmol) and stir. Add 5.04 g (40.0 mmol) of dimethyl sulfate to this. After 16 hours, the reaction mixture was poured into 200 ml of ice water, extracted with ether, and washed with water. After drying the ether layer with Glauber's salt and distilling off the solvent, 2.45 g of (-)-(2R * , 3S * )-2,3-epoxy-3-(4-methoxyphenyl)propionate methyl ester was obtained. Yield 58.9%
The instrumental data of IR and 1 HNMR completely matched that of Example 1. [α] 23 D -155° (c0.897, chloroform) bp 107-113°C/0.12 Torr Example 3 (-) -3-3.389g (18.0mmol) was suspended in 30ml of methylene chloride, and 2.00g of triethylamine was added.
(19.8mmol) and ethanol 0.91g
(19.8 mmol) and stir well. To this, 19.8 ml of the 1-methyl-2-chloropyridinium methyl sulfate solution obtained in Reference Example 3 was added at room temperature.
(19.8 mmol) gradually. After stirring the reaction solution overnight at room temperature, the solvent was distilled off under reduced pressure, new ethyl acetate was added, and the ethyl acetate layer was washed with water and then with saturated brine. After drying with Glauber's salt, the solvent was distilled off and the residue was distilled to give (-)-(2R * ,3S * )-2,3-epoxy-3-(4-methoxyphenyl)propionic acid ethyl ester 3.33 I got g. Yield 83.3g
bp110−111℃／2.5×10 -2 Torr〔α〕 23 D −152°
(c1.10, chloroform) IR (neat) cm -1 ; 2990, 2950, 2910, 2840,
1760, 1615, 1515, 1440, 1300, 1250, 1200,
1175, 1030, 835, 780 1 HNMR (CDCl 3 ) δ; 1.32 (t, 3H, J = 7
Hz, -OCH 2 CH 3 = 3.48 (d, 1H, J = 2Hz, epoxy ring proton) 3.80 (s, 3H, -OCH 3 =) 4.03 (d, 1H, J = 2Hz, epoxy ring proton) 4.27 (q , 2H, J = 7Hz, -OCH 2 = CH 3 6.87 (d, 2H, J = 8.8Hz, aromatic proton) 7.21 (d, 2H, J = 8.8Hz, aromatic proton)
Claims (1)
金属イオンを示す） で表わされる（−）−（2R*、3S*）−２、３−エポ
キシ−３−（４−メトキシフエニル）プロピオン
酸塩にR2SO4（式中Ｒは炭素数１〜４個の低級ア
ルキル基を示す）、又は１−メチル−２−ハロピ
リジニウム塩の存在化にROH（式中Ｒは前記と同
じ）を作用させることを特徴とする、一般式 （式中Ｒは前記と同じ） で表わされる（−）−（2R*、3S*）−２、３−エポ
キシ−３−（４−メトキシフエニル）プロピオン
酸エステルの製造法。[Claims] 1. General formula (-)-(2R * , 3S * )-2,3-epoxy-3-(4-methoxyphenyl)propionic acid represented by R 2 SO 4 (in the formula, R represents a lower alkyl group having 1 to 4 carbon atoms) in the salt, or ROH (in the formula, R is the same as above) in the presence of the 1-methyl-2-halopyridinium salt. A general formula characterized by acting on (wherein R is the same as above) A method for producing (-)-(2R * , 3S * )-2,3-epoxy-3-(4-methoxyphenyl)propionic ester.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP26743484A JPS61145174A (en) | 1984-12-20 | 1984-12-20 | Production method of novel optically active epoxypropionate derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP26743484A JPS61145174A (en) | 1984-12-20 | 1984-12-20 | Production method of novel optically active epoxypropionate derivative |
Related Child Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10199793A Division JPH06287183A (en) | 1993-04-05 | 1993-04-05 | Novel optically active epoxypropionate derivative |
| JP10199893A Division JPH06298751A (en) | 1993-04-05 | 1993-04-05 | Method for producing diltiazem hydrochloride |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61145174A JPS61145174A (en) | 1986-07-02 |
| JPH0428268B2 true JPH0428268B2 (en) | 1992-05-13 |
Family
ID=17444788
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP26743484A Granted JPS61145174A (en) | 1984-12-20 | 1984-12-20 | Production method of novel optically active epoxypropionate derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61145174A (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4885375A (en) * | 1988-05-18 | 1989-12-05 | Marion Laboratories, Inc. | Resolution of 3-(4-methoxyphenyl)glycidic acid with in situ conversion to alkyl esters |
| US5008411A (en) * | 1988-05-24 | 1991-04-16 | Hoffmann-La Roche Inc. | Glycidic acid ester and process of preparation |
| FR2637285B1 (en) * | 1988-10-03 | 1991-04-12 | Synthelabo | PROCESS FOR THE PREPARATION OF PROPIONIC ACID DERIVATIVES AND PRODUCTS OBTAINED |
| USRE34935E (en) * | 1989-01-11 | 1995-05-09 | Synthelabo | Method for preparing (+)-(2S,3S)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-5H-1,5-benzothiazepine-4-one and chlorinated derivatives thereof |
| FR2641535B1 (en) * | 1989-01-11 | 1991-03-15 | Synthelabo | PROCESS FOR THE PREPARATION OF (+) - (2S, 3S) -HYDROXY-3 (METHOXY-4 PHENYL) -2 DIHYDRO-2,3 5H-BENZOTHIAZEPINE-1,5 ONE-4 |
| FR2658513B1 (en) * | 1990-02-21 | 1994-02-04 | Rhone Poulenc Sante | PROCESS FOR THE PREPARATION OF CIS-BETA-PHENYLGLYCIDIC- (2R, 3R) ACID. |
| IL123352A0 (en) | 1997-02-27 | 1998-09-24 | Tanabe Seiyaku Co | Process for preparing an optically active trans-3-substituted glycidic acid ester |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59196881A (en) * | 1983-04-21 | 1984-11-08 | Shionogi & Co Ltd | Novel epoxide derivative |
| JPS6013776A (en) * | 1983-07-05 | 1985-01-24 | Sawai Seiyaku Kk | Production of optically active 3-(p-alkoxyphenyl)-glycidic acid derivative |
-
1984
- 1984-12-20 JP JP26743484A patent/JPS61145174A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS61145174A (en) | 1986-07-02 |
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