(2S,4R)-1-propyl-2-(3-aminopropyl)-4-(4-fluorobenzyl)piperidine | 916489-22-0

• 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,4R)-1-propyl-2-(3-aminopropyl)-4-(4-fluorobenzyl)piperidine
• 英文别名: 3-[(2S,4R)-4-[(4-fluorophenyl)methyl]-1-propylpiperidin-2-yl]propan-1-amine
• CAS: 916489-22-0
• 化学式: C₁₈H₂₉FN₂
• 分子量: 292.44
• InChiKey: ZMAMKAPQMAUDJN-WMZOPIPTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S,4R)-1-propyl-2-(3-aminopropyl)-4-(4-fluorobenzyl)piperidine 、 异氰酸3-乙酰基苯酯 以 二氯甲烷 为溶剂， 以96%的产率得到IS811
  参考文献：
  名称：

  Strategy for the Enantioselective Synthesis of trans-2,4-Disubstituted Piperidines:  Application to the CCR3 Antagonist IS811

  摘要：

  A strategy for the enantioselective synthesis of trans-2,4-disubstituted piperidines is proposed and applied to the preparation of IS811, a potent CCR3 antagonist. The C2 stereocenter is derived from commercial (R)-epichlorohydrin, while the C4 stereocenter is installed via diastereoselective hydrogenation of an alpha,beta-unsaturated lactone intermediate. Inversion of the original stereocenter via an efficient intramolecular S(N)2 amination affords the piperidine core of IS811. An improved protocol for the lithiation of ethyl propiolate is reported.

  DOI：

  10.1021/jo0616963
• 作为产物：
  描述：

  4-氟苄基氯化镁 在 Pt/Al₂O₃ sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 氢气 、 三乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 叔丁醇 为溶剂， -30.0~20.0 ℃ 、344.74 kPa 条件下， 反应 40.17h， 生成 (2S,4R)-1-propyl-2-(3-aminopropyl)-4-(4-fluorobenzyl)piperidine
  参考文献：
  名称：

  Strategy for the Enantioselective Synthesis of trans-2,4-Disubstituted Piperidines:  Application to the CCR3 Antagonist IS811

  摘要：

  A strategy for the enantioselective synthesis of trans-2,4-disubstituted piperidines is proposed and applied to the preparation of IS811, a potent CCR3 antagonist. The C2 stereocenter is derived from commercial (R)-epichlorohydrin, while the C4 stereocenter is installed via diastereoselective hydrogenation of an alpha,beta-unsaturated lactone intermediate. Inversion of the original stereocenter via an efficient intramolecular S(N)2 amination affords the piperidine core of IS811. An improved protocol for the lithiation of ethyl propiolate is reported.

  DOI：

  10.1021/jo0616963

文献信息

• Strategy for the Enantioselective Synthesis of <i>trans</i>-2,4-Disubstituted Piperidines:  Application to the CCR3 Antagonist IS811
  作者：Goss S. Kauffman、Paul S. Watson、William A. Nugent

  DOI：10.1021/jo0616963

  日期：2006.11.1

  A strategy for the enantioselective synthesis of trans-2,4-disubstituted piperidines is proposed and applied to the preparation of IS811, a potent CCR3 antagonist. The C2 stereocenter is derived from commercial (R)-epichlorohydrin, while the C4 stereocenter is installed via diastereoselective hydrogenation of an alpha,beta-unsaturated lactone intermediate. Inversion of the original stereocenter via an efficient intramolecular S(N)2 amination affords the piperidine core of IS811. An improved protocol for the lithiation of ethyl propiolate is reported.