(3S,4S)-4-苄基哌啶-3-醇 | 312625-28-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: (3S,4S)-4-苄基哌啶-3-醇
• 英文名称: (3S,4S)-4-benzylpiperidin-3-ol
• CAS: 312625-28-8
• 化学式: C₁₂H₁₇NO
• 分子量: 191.273
• InChiKey: DTNACGVJQYLRDI-VXGBXAGGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(2-chloroethanesulfonyl)phenol 、 (3S,4S)-4-苄基哌啶-3-醇 以85%的产率得到(3S,4S)-4-benzyl-1-[2-(4-hydroxybenzenesulfonyl)ethyl]piperidin-3-ol
  参考文献：
  名称：

  Efficient Enantioselective Formal Synthesis of Ro 67-8867, a NMDA 2B Receptor Antagonist

  摘要：

  通过7个步骤实现了Ro 67-8867的高效对映选择性形式合成，其中关键步骤包括氨基-锌-烯-烯醇环化和取代脯氨醇的对映选择性环化。

  DOI：

  10.1055/s-2005-865225
• 作为产物：
  描述：

  3-benzylpent-4-enoic acid 在 sodium azide 、 (S,S)-(salen)cobalt(III)(OAc) 、 dimethyl sulfide borane 、 水 、 氢气 、 碘 、 palladium(II) hydroxide 、 sodium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 75.0h， 生成 (3S,4S)-4-苄基哌啶-3-醇
  参考文献：
  名称：

  通过两个3位取代的环氧酯的立体中心HKR 光学纯净的γ-丁内酯和环氧酯：（-）-帕罗西汀，Ro 67-8867和（+）-依加多醇的正式合成†

  摘要：

  外消旋的HKR抗-或顺式-3-取代的环氧酯通过将Co（催化III salen络合物）提供到相应的对映体富集3,4-二取代γ丁内酯和3-取代的环氧酯随时获得。该策略已成功用于生物学活性的3,4-二取代哌啶衍生物（-）-帕罗西汀和Ro 67-8867以及天然产物（+）-依加醇化物的形式合成中。

  DOI：

  10.1039/c3ob27321k

文献信息

• Ethanesulfonyl-piperidine derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US06310213B1

  公开（公告）日：2001-10-30

  The invention relates to compounds of the general formula wherein R1 signifies hydrogen or hydroxy; R2 signifies hydrogen or methyl; and X signifies —O— or —CH2— and their pharmaceutically acceptable acid addition salts. It has been shown that these compounds have a good affitity to the NMDA receptor and they are therefore useful in the treatment of diseases, wherein the therapeutic indications include acute forms of neurodegeneration caused, e.g., by stroke or brain trauma; chronic forms of neurodegeneration such as Alzheimer's disease, Parkinson's disease, Huntington's disease or ALS (amyotrophic lateral sclerosis); neurodegeneration associated with bacterial or viral infections, and, diseases such as schizophrenia, anxiety, depression and chronic/acute pain.

  本发明涉及一般式化合物，其中R1表示氢或羟基；R2表示氢或甲基；X表示—O—或—CH2—及其药学上可接受的酸加盐。已经证明这些化合物与NMDA受体有很好的亲和力，因此它们在治疗疾病方面非常有用，其中治疗指标包括急性神经退化的形式，例如中风或脑外伤引起的急性神经退化；慢性神经退化，如阿尔茨海默病、帕金森病、亨廷顿病或ALS（肌萎缩侧索硬化症）；与细菌或病毒感染相关的神经退化，以及精神分裂症、焦虑、抑郁和慢性/急性疼痛等疾病。
• 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。
• Efficient Enantioselective Synthesis of the NMDA 2B Receptor Antagonist Ro 67-8867
  作者：Michelangelo Scalone、Pius Waldmeier

  DOI：10.1021/op034006v

  日期：2003.5.1

  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.
• ETHANESULFONYL-PIPERIDINE DERIVATIVES
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1189886A1

  公开（公告）日：2002-03-27