(2S,3R)-1-benzyl-3-chloro-2-phenylpiperidine

• 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: (2S,3R)-1-benzyl-3-chloro-2-phenylpiperidine
• 化学式: C₁₈H₂₀ClN
• 分子量: 285.817
• InChiKey: BJNYCWUMBXHMCV-MSOLQXFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (2S,3R)-1-benzyl-3-chloro-2-phenylpiperidine 在 sodium azide 、 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 55.0 ℃ 、413.7 kPa 条件下， 反应 53.0h， 生成 1-{(R)-[(S)-1-benzylpyrrolidin-2-yl](phenyl)methyl}-3-phenylthiourea
  参考文献：
  名称：

  Synthesis of Versatile Bifunctional Derivatives of Chiral Diamines Obtained through Anchimerically Assisted Nucleophilic Substitution Reactions on Diastereomeric Phenylprolinols

  摘要：

  Diastereomeric [(S)-1-benzylpyrrolidin-2-yl]-(R)-[(phenyl)methanamine] and [(S)-1-benzylpyrrolidin-2-yl]-(S)-[(phenyl)methanamine], were synthesized by selective internal backside nucleophilic substitution of the corresponding activated phenylprolinols. X-Ray diffraction structures of crystalline acetamide derivatives confirmed the anticipated stereochemistry for a S(N)ib reaction mechanism. In order to apply this reaction to the synthesis of bifunctional analogs, a series of fragments such as a thiourea moiety and sulfonamide functions were introduced for the functionalization of the primary amino group in the substrate, obtaining more stable and potentially useful derivatives.

  DOI：

  10.3987/com-12-s(n)82
• 作为产物：
  描述：

  N-benzyl-(S)-proline methyl ester 在 lithium aluminium tetrahydride 、 草酰氯 、 magnesium 、 二甲基亚砜 、 甲基磺酰氯 、 三乙胺 、 lithium bromide 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 21.33h， 生成 (2S,3R)-1-benzyl-3-chloro-2-phenylpiperidine
  参考文献：
  名称：

  Synthesis of Versatile Bifunctional Derivatives of Chiral Diamines Obtained through Anchimerically Assisted Nucleophilic Substitution Reactions on Diastereomeric Phenylprolinols

  摘要：

  Diastereomeric [(S)-1-benzylpyrrolidin-2-yl]-(R)-[(phenyl)methanamine] and [(S)-1-benzylpyrrolidin-2-yl]-(S)-[(phenyl)methanamine], were synthesized by selective internal backside nucleophilic substitution of the corresponding activated phenylprolinols. X-Ray diffraction structures of crystalline acetamide derivatives confirmed the anticipated stereochemistry for a S(N)ib reaction mechanism. In order to apply this reaction to the synthesis of bifunctional analogs, a series of fragments such as a thiourea moiety and sulfonamide functions were introduced for the functionalization of the primary amino group in the substrate, obtaining more stable and potentially useful derivatives.

  DOI：

  10.3987/com-12-s(n)82

文献信息

• Synthesis of Diastereomeric Pyrrolidine Sulfamides via Anchimerically Assisted Nucleophilic Substitution Reactions
  作者：Jorge Vargas-Caporali、Arie van der Lee、Georges Dewynter、Eusebio Juaristi

  DOI：10.2174/1570178615666180110162202

  日期：2018.4.12

  type of diastereomeric amino alcohols to the above-mentioned nucleophile usually leads to the formation of piperidines via ring expansion, either through classical nucleophilic substitution or the Mitsunobu version, only the pyrrolidine derivatives were generated with retention of configuration on the exocyclic stereocenter, owing to the neighboring group participation (internal backside nucleophilic

  在开发方便的合成路线的关键步骤中，Mitsunobu反应用于从（R）-或（S）-[（S）-1-苄基吡咯烷丁-2-基]（）对映选择性制备吡咯烷-磺酰胺配体苯基）甲醇，并使用叔丁基吡咯烷-1--1-基磺酰基氨基甲酸酯作为非常规亲核源。尽管有充分的文献证明，这类非对映体氨基醇暴露于上述亲核试剂通常会导致环扩环形成哌啶，无论是通过经典亲核取代还是Mitsunobu版本，只有吡咯烷衍生物得以保留由于邻近基团的参与（内部背面亲核取代，SNib），在环外立体中心的构型改变。
• Stereoselective synthesis of (2S,3S)-3-hydroxy-2-phenylpiperidines, precursors of non-peptidic substance P antagonists
  作者：Olivier Calvez、Nicole Langlois

  DOI：10.1016/s0040-4039(99)01462-8

  日期：1999.9

  (2S)-N-Boc-3-oxo-2-phenylpiperidine 5 and (2S,3S)-N-Boc-3-hydroxy-2-phenylpiperidine 6, known chiral building blocks for the synthesis of non-peptidic substance P antagonists, were prepared from erythro (2S)-N-benzyl 2-hydroxybenzylpyrrolidine derived from (S)-N-methoxy-N-methylpyroglutamide. (C) 1999 Elsevier Science Ltd. All rights reserved.

  (S)-N-Boc-3-酮-2-苯基哌啶（5）和(S,S)-N-Boc-3-羟基-2-苯基哌啶（6），这两种已知的手性构建单元，用于合成非肽类物质P拮抗剂，是从由(S)-N-甲氧基-N-甲基吡咯烷四肽衍生而来的赤藓糖醇-(2S)-N-苄基-2-羟基苯甲酰基吡咯啶制备得到的。©1999 Elsevier Science Ltd. 保留所有权利。
• Enantioselective synthesis of 2,3-disubstituted piperidines from (S)-methylpyroglutamate
  作者：Olivier Calvez、Angèle Chiaroni、Nicole Langlois

  DOI：10.1016/s0040-4039(98)02190-x

  日期：1998.12

  N-methoxy-N-methylamide derived from (S)-methylpyroglutamate was prepared in good yield and allowed the addition of Grignard reagents. Erythro (2S)-1-benzyl-2-hydroxybenzyl pyrrolidine obtained by this way was converted into (2S,3R)-1-benzyl-3-hydroxy-2-phenylpiperidine and its chloro analog.

  以高收率制备衍生自（S）-甲基焦谷氨酸的N-甲氧基-N-甲基酰胺，并加入格氏试剂。将由此获得的赤型（2S）-1-苄基-2-羟基苄基吡咯烷转化为（2S，3R）-1-苄基-3-羟基-2-苯基哌啶及其氯代类似物。