(3S,4S)-1,4-dibenzylpiperidin-3-ol

• 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: (3S,4S)-1,4-dibenzylpiperidin-3-ol
• 英文别名: (S,S)-cis-1,4-dibenzyl-piperidin-3-ol；(3S,4S)-1,4-dibenzyl-piperidine-3-ol
• 化学式: C₁₉H₂₃NO
• 分子量: 281.398
• InChiKey: BLDUXBUGLHPHTL-RTBURBONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3S,4S)-1,4-dibenzylpiperidin-3-ol 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以9.7 g的产率得到(3S,4S)-4-苄基哌啶-3-醇
  参考文献：
  名称：

  Efficient Enantioselective Synthesis of the NMDA 2B Receptor Antagonist Ro 67-8867

  摘要：

  An efficient, enantioselective, and scalable eight-step synthesis for the NMDA 2B receptor antagonist Ro 67-8867 (S,S)-1 selected for the treatment of acute ischemic stroke is described based on the coupling reaction of the amino alcohol (S,S)-6 with the sulfone building block 7. The synthesis of the amino alcohol (S,S)-6 was achieved by the highly selective asymmetric hydrogenation of the piperidinone 4*HCl proceeding with concomitant dynamic kinetic resolution to (S,S)-5. Subsequent debenzylation afforded the enantiomerically pure amino alcohol (S,S)-6 after ee-enhancement by simple crystallization in good yield. The hydrogenation substrate 4*HCl was prepared as a stable hydrochloride in two steps from ethyl N-benzyl-3-oxo-4-piperidinecarboxylate hydrochloride (2) for which a new, short, efficient, and cheap synthesis was developed. To bypass a mutagenic intermediate, a revised safe protocol for the sulfone building block 7 was established. The new synthesis allows the access to Ro 67-8867 (S,S)-1 in an overall yield of 53% compared to 3.5% of the Discovery Chemistry approach.

  DOI：

  10.1021/op034006v
• 作为产物：
  描述：

  N-苄基甘氨酸乙酯 在 盐酸 、 potassium tert-butylate 、 sodium ethanolate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 水 、 异丙醇 、 甲苯 为溶剂， 85.0 ℃ 、4.0 MPa 条件下， 反应 27.67h， 生成 (3S,4S)-1,4-dibenzylpiperidin-3-ol
  参考文献：
  名称：

  Efficient Enantioselective Synthesis of the NMDA 2B Receptor Antagonist Ro 67-8867

  摘要：

  An efficient, enantioselective, and scalable eight-step synthesis for the NMDA 2B receptor antagonist Ro 67-8867 (S,S)-1 selected for the treatment of acute ischemic stroke is described based on the coupling reaction of the amino alcohol (S,S)-6 with the sulfone building block 7. The synthesis of the amino alcohol (S,S)-6 was achieved by the highly selective asymmetric hydrogenation of the piperidinone 4*HCl proceeding with concomitant dynamic kinetic resolution to (S,S)-5. Subsequent debenzylation afforded the enantiomerically pure amino alcohol (S,S)-6 after ee-enhancement by simple crystallization in good yield. The hydrogenation substrate 4*HCl was prepared as a stable hydrochloride in two steps from ethyl N-benzyl-3-oxo-4-piperidinecarboxylate hydrochloride (2) for which a new, short, efficient, and cheap synthesis was developed. To bypass a mutagenic intermediate, a revised safe protocol for the sulfone building block 7 was established. The new synthesis allows the access to Ro 67-8867 (S,S)-1 in an overall yield of 53% compared to 3.5% of the Discovery Chemistry approach.

  DOI：

  10.1021/op034006v

文献信息

• Process for the preparation of ethanesul fonyl-piperidine derivatives
  申请人：——

  公开号：US20010037026A1

  公开（公告）日：2001-11-01

  The present invention relates to a new process for the preparation of compounds of the formulae 1 and their pharmaceutically acceptable acid addition salts, which are NMDA (N-methyl-D-aspartate)-receptor-subtype selective blockers.

  本发明涉及一种制备式1化合物及其药学上可接受的酸盐的新工艺，该化合物为NMDA（N-甲基-D-天门冬氨酸）受体亚型选择性阻滞剂。
• Piperidine and piperazine compounds for use in the treatment of Alzheimer
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1136475A1

  公开（公告）日：2001-09-26

  The present invention relates to a new process for the preparation of compounds of the general formulae wherein R1- R4are, independently from each other, hydrogen, halogen, hydroxy, amino, nitro, lower-alkyl-sulfonylamido, or acetamido; R5-R8are, independently from each other hydrogen, lower-alkyl, halogen, trifluoromethyl or lower-alkoxy;    and their pharmaceutically acceptable acid addition salts. The compounds of formulae I-a and I-b are NMDA (N-methyl-D-aspartate)-receptor-subtype selective blockers, which have a key function in modulating neuronal activity and plasticity which makes them key players in mediating processes underlying development of CNS including learning and memory formation and function.

  本发明涉及一种制备通式如下化合物的新工艺 其中 R1- R4互为氢、卤素、羟基、氨基、硝基、低级烷基磺酰氨基或乙酰氨基； R5-R8 相互独立地为氢、低级烷基、卤素、三氟甲基或低级烷氧基； 及其药学上可接受的酸加成盐。 式 I-a 和 I-b 的化合物是 NMDA（N-甲基-D-天冬氨酸）受体亚型选择性阻断剂，具有调节神经元活性和可塑性的关键功能，这使它们成为介导中枢神经系统发育过程（包括学习和记忆的形成和功能）的关键角色。
• ETHANESULFONYL-PIPERIDINE DERIVATIVES
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1189886B1

  公开（公告）日：2006-01-04
• PRODRUGS TO NMDA RECEPTOR LIGANDS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1313703B1

  公开（公告）日：2008-02-13
• US6310213B1
  申请人：——

  公开号：US6310213B1

  公开（公告）日：2001-10-30