tert-butyl 4-[(1RS)-1-(3,4-dichlorophenyl)-2-hydroxyethyl]piperidine-1-carboxylate | 1207438-71-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-[(1RS)-1-(3,4-dichlorophenyl)-2-hydroxyethyl]piperidine-1-carboxylate
• 英文别名: Tert-butyl 4-[1-(3,4-dichlorophenyl)-2-hydroxyethyl]piperidine-1-carboxylate
• CAS: 1207438-71-8
• 化学式: C₁₈H₂₅Cl₂NO₃
• 分子量: 374.307
• InChiKey: ZHZCHPHWIWDXKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[(1RS)-1-(3,4-dichlorophenyl)-2-hydroxyethyl]piperidine-1-carboxylate 在 戴斯-马丁氧化剂 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以76%的产率得到tert-butyl 4-(1-(3,4-dichlorophenyl)-2-oxoethyl)piperidine-1-carboxylate
  参考文献：
  名称：

  Preparation of (S)-4-(1-(3,4-dichlorophenyl)-2-methoxyethyl)piperidine

  摘要：

  The novel triple reuptake inhibitor (S)-4-(1-(3,4-dichlorophenyl)-2-methoxyethyl)piperidine monohydrochloride 1 possesses a unique 2-phenyl-2-(piperidin-4-yl)ethanol moiety with a stereogenic center at the benzyl position. To synthesize 1 as the (S)-isomer, three possible routes were investigated; (1) the lipase-catalyzed kinetic resolution of tert-butyl 4-(1-(3,4-dichlorophenyl)-2-hydroxyethyl)piperidine-1-carboxylate 2 utilizing PS-IM from Pseudomonas sp. as the lipase; (2) the asymmetric hydrogenation of tert-butyl 4-(1-(3,4-dichlorophenyl)-2-oxoethyl)piperidine-1-carboxylate 5 utilizing dynamic kinetic resolution; and (3) the resolution of racemic [1-(tert-butoxycarbonyl)piperidin-4yl](3,4-dichlorophenyl)acetic acid 8 with (S)-phenylethylamine. The design of the asymmetric reaction using retrosynthesis, as well as the extensive exploration of enzymes, asymmetric hydrogenation catalysts, and resolving reagents, were all important to afford the optically active compound 1 in excellent yield. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2015.06.021
• 作为产物：
  描述：

  (2RS)-2-[1-(tert-butoxycarbonyl)piperidin-4-yl]-2-(3,4-dichlorophenyl)ethanoic acid 在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 以69%的产率得到tert-butyl 4-[(1RS)-1-(3,4-dichlorophenyl)-2-hydroxyethyl]piperidine-1-carboxylate
  参考文献：
  名称：

  Novel triple reuptake inhibitors with low risk of CAD associated liabilities: Design, synthesis and biological activities of 4-[(1S)-1-(3,4-dichlorophenyl)-2-methoxyethyl]piperidine and related compounds

  摘要：

  A novel triple reuptake inhibitor with low potential of liabilities associated with cationic amphiphilic drug (CAD) was identified following an analysis of existing drugs. Low molecular weight (MW < ca. 300), low aromatic ring count (number = 1) and reduced lipophilicity (ClogP < 3.5) were hypothesized to be key factors to avoid the CAD associated liabilities (CYP2D6 inhibition, hERG inhibition and phospholipidosis). Based on the hypothesis, a series of piperidine compounds was designed with consideration of the common characteristic features of CNS drugs. Optimization of the side chain by adjusting overall lipophilicity suggested that incorporation of a methoxymethyl group could provide compounds with a balance of both potent reuptake inhibition and low liability potential. Compound (S)-3a showed a potent antidepressant-like effect in the mice tail suspension test (MED = 10 mg/kg, p.o.), proportional monoamine transporter occupancies and enhancement of monoamine concentrations in mouse prefrontal cortex. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.025