(R)-1-[(1R,2R,3S)-3-{(R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy}-2-(4-fluorophenyl)cyclopentylmethyl]piperidine-3-carboxylic acid tert-butyl ester | 912807-36-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-1-[(1R,2R,3S)-3-{(R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy}-2-(4-fluorophenyl)cyclopentylmethyl]piperidine-3-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (3R)-1-[[(1R,2R,3S)-3-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-2-(4-fluorophenyl)cyclopentyl]methyl]piperidine-3-carboxylate
• CAS: 912807-36-4
• 化学式: C₃₂H₃₈F₇NO₃
• 分子量: 617.647
• InChiKey: UFDCKHFCZXGHFB-JEPPUSMKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  43
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (R)-1-[(1R,2R,3S)-3-{(R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy}-2-(4-fluorophenyl)cyclopentylmethyl]piperidine-3-carboxylic acid tert-butyl ester 在 三氟乙酸 、 盐酸 作用下， 以 1,2-二氯乙烷 、 乙醚 为溶剂， 反应 15.5h， 以85%的产率得到(R)-1-[(1R,2R,3S)-3-{(R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy}-2-(4-fluorophenyl)cyclopentylmethyl]piperidine-3-carboxylic acid hydrochloride
  参考文献：
  名称：

  Stereoselective Preparation of a Cyclopentane-Based NK1 Receptor Antagonist Bearing an Unsymmetrically Substituted Sec−Sec Ether

  摘要：

  A highly efficient synthesis of the potent and selective NK-1 receptor antagonist 1 is described. The key transformation involved the etherification reaction between cyclopentanol 12 and chiral imidate 30 which was catalyzed by HBF4 to initially give ether 14 as a 17:1 mixture of diastereomers and in 75% combined yield. The diastereoselectivity was upgraded to 109:1 by crystallization of the triethylamine solvate 44 which was isolated in 54% yield from 12. Mechanistic studies confirmed that the etherification reaction proceeds through an unprecedented S(N)2 reaction pathway under typical S(N)1 reaction conditions.

  DOI：

  10.1021/jo061268x
• 作为产物：
  描述：

  (1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl 2,2,2-trichloroethanimidate 在 tetrafluoroboric acid 、 硼烷四氢呋喃络合物 、 N,N-二异丙基乙胺 、 甲基磺酸酐 作用下， 以 正庚烷 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 24.25h， 生成 (R)-1-[(1R,2R,3S)-3-{(R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy}-2-(4-fluorophenyl)cyclopentylmethyl]piperidine-3-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Stereoselective Preparation of a Cyclopentane-Based NK1 Receptor Antagonist Bearing an Unsymmetrically Substituted Sec−Sec Ether

  摘要：

  A highly efficient synthesis of the potent and selective NK-1 receptor antagonist 1 is described. The key transformation involved the etherification reaction between cyclopentanol 12 and chiral imidate 30 which was catalyzed by HBF4 to initially give ether 14 as a 17:1 mixture of diastereomers and in 75% combined yield. The diastereoselectivity was upgraded to 109:1 by crystallization of the triethylamine solvate 44 which was isolated in 54% yield from 12. Mechanistic studies confirmed that the etherification reaction proceeds through an unprecedented S(N)2 reaction pathway under typical S(N)1 reaction conditions.

  DOI：

  10.1021/jo061268x

文献信息

• Stereoselective Preparation of a Cyclopentane-Based NK1 Receptor Antagonist Bearing an Unsymmetrically Substituted Sec−Sec Ether
  作者：Jeffrey T. Kuethe、Jean-Francois Marcoux、Audrey Wong、Jimmy Wu、Michael C. Hillier、Peter G. Dormer、Ian W. Davies、David L. Hughes

  DOI：10.1021/jo061268x

  日期：2006.9.1

  A highly efficient synthesis of the potent and selective NK-1 receptor antagonist 1 is described. The key transformation involved the etherification reaction between cyclopentanol 12 and chiral imidate 30 which was catalyzed by HBF4 to initially give ether 14 as a 17:1 mixture of diastereomers and in 75% combined yield. The diastereoselectivity was upgraded to 109:1 by crystallization of the triethylamine solvate 44 which was isolated in 54% yield from 12. Mechanistic studies confirmed that the etherification reaction proceeds through an unprecedented S(N)2 reaction pathway under typical S(N)1 reaction conditions.