(4-chloro-3-methylphenyl) (2R,3S)-3-(4-methoxyphenyl)oxirane-2-carboxylate | 154169-78-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: (4-chloro-3-methylphenyl) (2R,3S)-3-(4-methoxyphenyl)oxirane-2-carboxylate
• CAS: 154169-78-5
• 化学式: C₁₇H₁₅ClO₄
• 分子量: 318.757
• InChiKey: LAUPJFHHHDUNNR-JKSUJKDBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  48.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4-chloro-3-methylphenyl) (2R,3S)-3-(4-methoxyphenyl)oxirane-2-carboxylate 在 甲烷磺酸 、 三氯化铁 作用下， 以 甲醇 、 氯苯 为溶剂， 反应 7.08h， 生成 (2S-cis)-(+)-2,3-二氢-3-羟基-2-(4-甲氧苯基)-1,5-苯并硫氮杂卓-4(5H)-酮
  参考文献：
  名称：

  First practical resolution of a 3-(4-methoxyphenyl)glycidic acid ester by preferential crystallization and synthesis of diltiazem

  摘要：

  Among the various esters of 3-(4-methoxyphenyl)glycidic acid, 4-chloro-3-methylphenyl ester (+/-)-3 was found to exist as a conglomerate, and could be alternately resolved into (+)- and (-)-3 of >98% ee by a preferential crystallization procedure. Furthermore, a 1,5-benzothiazepine derivative, (+)-6, a significant intermediate of diltiazem, was prepared in one pot in 76% overall yield through the treatment of enantiomerically pure (-)-3 with 2-aminothiophenol followed by a ring closing reaction. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(98)00148-7
• 作为产物：
  描述：

  4-氯-3-甲基苯酚 在 三乙胺 、 2-chloro-1-methylpyridinium sulfate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 (4-chloro-3-methylphenyl) (2R,3S)-3-(4-methoxyphenyl)oxirane-2-carboxylate
  参考文献：
  名称：

  First practical resolution of a 3-(4-methoxyphenyl)glycidic acid ester by preferential crystallization and synthesis of diltiazem

  摘要：

  Among the various esters of 3-(4-methoxyphenyl)glycidic acid, 4-chloro-3-methylphenyl ester (+/-)-3 was found to exist as a conglomerate, and could be alternately resolved into (+)- and (-)-3 of >98% ee by a preferential crystallization procedure. Furthermore, a 1,5-benzothiazepine derivative, (+)-6, a significant intermediate of diltiazem, was prepared in one pot in 76% overall yield through the treatment of enantiomerically pure (-)-3 with 2-aminothiophenol followed by a ring closing reaction. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(98)00148-7

文献信息

• Process for preparing optically active trans-3-substituted glycidic acid ester
  申请人：TANABE SEIYAKU CO., LTD.

  公开号：EP0861834A1

  公开（公告）日：1998-09-02

  A process for preparing an optically active trans-3-substituted glycidic acid ester compound of the formula (I): wherein ring A is a substituted or unsubstituted benzene ring, and R1 is an ester residue, which comprises: preparing a solution of one optical isomer (A) and the other optical isomer (B) of the ester compound (I), both of which are the optical isomers due to the asymmetric carbons at 2- and 3-positions, and an ester compound (B') which is different from the isomer (B) only in the ester residue R1, crystallizing the optical isomer (A) from the solution up to the extent that the optical isomer (A) is crystallized without the precipitation of the optical isomer (B) due to the presence of the ester compound (B') though the optical isomer (B) would precipitate if the ester compound (B') were not present, and isolating the crystals of the optical isomer (A), whereby a desired optical isomer (A) can be obtained in high purity and in a high yield such that the desired isomer can be crystallized until the concentration of the desired isomer in the mother liquor becomes very low as compared with conventional processes.

  一种制备具有光学活性的反式-3-取代缩水甘油酸酯类化合物的工艺，其式为 (I)： 其中环 A 是取代或未取代的苯环，R1 是酯残基，它包括 制备酯化合物（I）的一种光学异构体（A）和另一种光学异构体（B）的溶液，这两种光学异构体都是由于 2 位和 3 位上的碳不对称而形成的光学异构体，以及一种酯化合物（B'），该酯化合物（B'）仅在酯残基 R1 上与异构体（B）不同、 从溶液中结晶出光学异构体（A），结晶程度以光学异构体（A）不因酯类化合物（B'）的存在而析出光学异构体（B）为限，尽管如果没有酯类化合物（B'），光学异构体（B）也会析出，以及 分离出光学异构体（A）的晶体，从而获得高纯度和高产率的所需光学异构体（A），使所需异构体可以结晶，直到母液中的所需异构体浓度与传统工艺相比变得非常低。
• US5998637A
  申请人：——

  公开号：US5998637A

  公开（公告）日：1999-12-07
• US6197953B1
  申请人：——

  公开号：US6197953B1

  公开（公告）日：2001-03-06
• First practical resolution of a 3-(4-methoxyphenyl)glycidic acid ester by preferential crystallization and synthesis of diltiazem
  作者：Shin-ichi Yamada、Katsuji Morimatsu、Ryuzo Yoshioka、Yasuhiko Ozaki、Hiroyasu Seko

  DOI：10.1016/s0957-4166(98)00148-7

  日期：1998.5

  Among the various esters of 3-(4-methoxyphenyl)glycidic acid, 4-chloro-3-methylphenyl ester (+/-)-3 was found to exist as a conglomerate, and could be alternately resolved into (+)- and (-)-3 of >98% ee by a preferential crystallization procedure. Furthermore, a 1,5-benzothiazepine derivative, (+)-6, a significant intermediate of diltiazem, was prepared in one pot in 76% overall yield through the treatment of enantiomerically pure (-)-3 with 2-aminothiophenol followed by a ring closing reaction. (C) 1998 Elsevier Science Ltd. All rights reserved.