1-tert-butyl 3-methyl (3R,4R)-4-(3-ethyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate | 1207065-49-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1-tert-butyl 3-methyl (3R,4R)-4-(3-ethyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate
• CAS: 1207065-49-3
• 化学式: C₂₁H₂₉N₃O₅
• 分子量: 403.478
• InChiKey: LUBPTWIRFVXUER-HUUCEWRRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.79
• 重原子数：
  29.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  82.77
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  环辛烷甲醛 、 1-tert-butyl 3-methyl (3R,4R)-4-(3-ethyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate 在 盐酸 、 三乙酰氧基硼氢化钠 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以80%的产率得到(+/-)-trans-1-(cyclooctylmethyl)-4-(3-ethyl-2-oxo-2,3-dihydrobenzoimidazol-1-yl)piperidine-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Efficient and practical asymmetric synthesis of 1-tert-butyl 3-methyl (3R,4R)-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate, a useful intermediate for the synthesis of nociceptin antagonists

  摘要：

  An efficient and practical asymmetric synthesis of 1-tert-butyl 3-methyl (3R,4R)-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate 1, a useful intermediate for the synthesis of nociceptin antagonists, has been developed. This method includes the following key steps: (1) diastereoseiective reduction of a chiral enaminoester 3 having (R)-1-phenylethylamine as a chiral pool constituent with the use of a combined TFA-NaBH4 reduction system and (2) efficient isomerization from 3,4-cis-substituted piperidine 8 to 3,4-trans-substituted piperidine 1 under basic conditions. The above methods proved to be applicable for large-scale operation and hundred grams of enantiomerically pure compound 1 (>98% ee) was obtained. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tetasy.2009.07.046
• 作为产物：
  描述：

  1-tert-butyl 3-methyl (3R,4R)-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate 、 碘乙烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以96%的产率得到1-tert-butyl 3-methyl (3R,4R)-4-(3-ethyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate
  参考文献：
  名称：

  Efficient and practical asymmetric synthesis of 1-tert-butyl 3-methyl (3R,4R)-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate, a useful intermediate for the synthesis of nociceptin antagonists

  摘要：

  An efficient and practical asymmetric synthesis of 1-tert-butyl 3-methyl (3R,4R)-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate 1, a useful intermediate for the synthesis of nociceptin antagonists, has been developed. This method includes the following key steps: (1) diastereoseiective reduction of a chiral enaminoester 3 having (R)-1-phenylethylamine as a chiral pool constituent with the use of a combined TFA-NaBH4 reduction system and (2) efficient isomerization from 3,4-cis-substituted piperidine 8 to 3,4-trans-substituted piperidine 1 under basic conditions. The above methods proved to be applicable for large-scale operation and hundred grams of enantiomerically pure compound 1 (>98% ee) was obtained. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tetasy.2009.07.046