1-tert-butyl 3-methyl (3S,4R)-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate | 916347-43-8

• 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 (3S,4R)-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate
• 英文别名: 1-O-tert-butyl 3-O-methyl (3S,4R)-4-(2-oxo-3H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate
• CAS: 916347-43-8
• 化学式: C₁₉H₂₅N₃O₅
• 分子量: 375.425
• InChiKey: JFXMDLZHYCXDDZ-GXTWGEPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  88.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-tert-butyl 3-methyl (3S,4R)-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidine-1,3-dicarboxylate 在 sodium carbonate 作用下， 以 甲醇 为溶剂， 反应 18.0h， 以19.5 mg的产率得到1-tert-butyl 3-methyl (3R,4R)-4-(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
• 作为产物：
  描述：

  Carbonyldiimidazole 、 1-tert-butyl 3-methyl (3S,4R)-4-[(2-aminophenyl)amino]piperidine-1,3-dicarboxylate 以 氯仿 为溶剂， 反应 2.0h， 以49 mg的产率得到1-tert-butyl 3-methyl (3S,4R)-4-(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

文献信息

• 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
  作者：Hideki Jona、Jun Shibata、Masanori Asai、Yasuhiro Goto、Sachie Arai、Shigeru Nakajima、Osamu Okamoto、Hiroshi Kawamoto、Yoshikazu Iwasawa

  DOI：10.1016/j.tetasy.2009.07.046

  日期：2009.11

  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.