(S)-1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-(3,4,5-trimethoxyphenoxy)propan-2-ol | 68577-19-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (S)-1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-(3,4,5-trimethoxyphenoxy)propan-2-ol
• 英文别名: (S)-enciprazine；Enciprazine, (S)-；(2S)-1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-(3,4,5-trimethoxyphenoxy)propan-2-ol
• CAS: 68577-19-5
• 化学式: C₂₃H₃₂N₂O₆
• 分子量: 432.517
• InChiKey: KSQCNASWXSCJTD-KRWDZBQOSA-N

物化性质

• 沸点：
  611.5±55.0 °C(Predicted)
• 密度：
  1.171±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  72.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-hydroxy-3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl chloride 在 potassium carbonate 、 磷脂酶B 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 15.0h， 生成 (S)-1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-(3,4,5-trimethoxyphenoxy)propan-2-ol
  参考文献：
  名称：

  New chemical and chemo-enzymatic routes for the synthesis of (RS)- and (S)-enciprazine

  摘要：

  The chemo-enzymatic synthesis of racemic and enantiopure (RS)- and (S)-enciprazine 1, a non-benzodiazepine anxiolytic drug, is described herein. The synthesis started from 1-(2-methoxyphenyl) piperazine 3, which was treated with 2-(chloromethyl) oxirane (RS)-4 using lithium bromide to afford a racemic alcohol, 1-chloro-3-(4-(2-methoxyphenyl) piperazin-1-yl) propan-2-ol (RS)-6 in 85% yield. Intermediate (S)-6 was synthesized from racemic alcohol (RS)-6 using Candida rugosa lipase (CRL) with vinyl acetate as the acyl donor. Various reaction parameters such as temperature, time, substrate, enzyme concentration, and the effect of the reaction medium on the conversion and enantiomeric excess for the transesterification of (RS)-6 by CRL were optimized. It was observed that 10 mM of (RS)-6, 50 mg/mL of CRL in 4.0 mL of toluene with vinyl acetate (5.4 mmol) as acyl donor at 30 degrees C gave good conversion (C = 49.4%) and enantiomeric excess (ee(p) = 98.4% and ee(s) = 96%) after 9 h of reaction. Compound (S)-6 is a key intermediate for the synthesis of enantiopure (S)-1. The (RS)- and (S)-enciprazine drug 1 was synthesized by treating (RS)and (S)-6 with 3,4,5-trimethoxyphenol 5 using MeCN as a solvent and K2CO3 as a base. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2012.08.002

文献信息

• A Simple and Efficient Asymmetric Synthesis of Anxiolytic Drug Enciprazine
  作者：A. Narsaiah、B. Nagaiah

  DOI：10.1055/s-0030-1258173

  日期：2010.8

  A straightforward and efficient asymmetric synthesis of (S)-1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-(3,4,5-trimethoxyphen­oxy)propan-2-ol is described. The key intermediate, (S)-2-[(3,4,5-trimethoxyphenoxy)methyl]oxirane, was obtained by a hydrolytic kinetic resolution method using the catalyst (R,R)-salen-cobalt(III) complex. trimethoxyphenol - resolution - chiral epoxide - meth­oxy­benzenamine

  描述了（S）-1- [4-（2-甲氧基苯基）哌嗪-1-基] -3-（3,4,5-三甲氧基苯氧基）丙烷-2-醇的直接有效的不对称合成。通过水解动力学拆分方法，使用催化剂（R，R）-salen-钴（III）配合物，获得了关键中间体（S）-2-[（3,4,5-三甲氧基苯氧基）甲基]环氧乙烷。 三甲氧基苯酚-拆分-手性环氧化物-甲氧基苯甲胺
• New chemical and chemo-enzymatic routes for the synthesis of (RS)- and (S)-enciprazine
  作者：Linga Banoth、Thete Karuna Narayan、Uttam C. Banerjee

  DOI：10.1016/j.tetasy.2012.08.002

  日期：2012.9

  The chemo-enzymatic synthesis of racemic and enantiopure (RS)- and (S)-enciprazine 1, a non-benzodiazepine anxiolytic drug, is described herein. The synthesis started from 1-(2-methoxyphenyl) piperazine 3, which was treated with 2-(chloromethyl) oxirane (RS)-4 using lithium bromide to afford a racemic alcohol, 1-chloro-3-(4-(2-methoxyphenyl) piperazin-1-yl) propan-2-ol (RS)-6 in 85% yield. Intermediate (S)-6 was synthesized from racemic alcohol (RS)-6 using Candida rugosa lipase (CRL) with vinyl acetate as the acyl donor. Various reaction parameters such as temperature, time, substrate, enzyme concentration, and the effect of the reaction medium on the conversion and enantiomeric excess for the transesterification of (RS)-6 by CRL were optimized. It was observed that 10 mM of (RS)-6, 50 mg/mL of CRL in 4.0 mL of toluene with vinyl acetate (5.4 mmol) as acyl donor at 30 degrees C gave good conversion (C = 49.4%) and enantiomeric excess (ee(p) = 98.4% and ee(s) = 96%) after 9 h of reaction. Compound (S)-6 is a key intermediate for the synthesis of enantiopure (S)-1. The (RS)- and (S)-enciprazine drug 1 was synthesized by treating (RS)and (S)-6 with 3,4,5-trimethoxyphenol 5 using MeCN as a solvent and K2CO3 as a base. (C) 2012 Elsevier Ltd. All rights reserved.