3,5-bis(trifluoromethyl)benzoic acid (1S,2R,3R)-3-(tert-butyldimethylsilanyloxymethyl)-2-(4-fluorophenyl)cyclopentyl | 912807-20-6

• 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: 3,5-bis(trifluoromethyl)benzoic acid (1S,2R,3R)-3-(tert-butyldimethylsilanyloxymethyl)-2-(4-fluorophenyl)cyclopentyl
• CAS: 912807-20-6
• 化学式: C₂₇H₃₁F₇O₃Si
• 分子量: 564.616
• InChiKey: NUZMKQRTLMAACK-RTFZILSDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.6
• 重原子数：
  38.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  35.53
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3,5-bis(trifluoromethyl)benzoic acid (1S,2R,3R)-3-(tert-butyldimethylsilanyloxymethyl)-2-(4-fluorophenyl)cyclopentyl 在 palladium on activated charcoal 、 dimethyltitanocene 氢气 、 N,N-二异丙基乙胺 、 三氟乙酸 、 甲基磺酸酐 作用下， 以 乙酸乙酯 、 1,2-二氯乙烷 、 甲苯 为溶剂， 80.0 ℃ 、275.79 kPa 条件下， 反应 43.25h， 生成 (R)-1-[(1R,2R,3S)-3-{(R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy}-2-(4-fluorophenyl)cyclopentylmethyl]piperidine-3-carboxylic acid 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：

  methyl (1R,2R,3S)-2-(4-fluorophenyl)-3-hydroxycyclopentane-1-carboxylate 在 咪唑 、 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.5h， 生成 3,5-bis(trifluoromethyl)benzoic acid (1S,2R,3R)-3-(tert-butyldimethylsilanyloxymethyl)-2-(4-fluorophenyl)cyclopentyl
  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