cis-2-chloromethyl-1-(4-methylbenzyl)-4-phenylpiperidine-4-carbonitrile

• 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: cis-2-chloromethyl-1-(4-methylbenzyl)-4-phenylpiperidine-4-carbonitrile
• 英文别名: (2R,4S)-2-(chloromethyl)-1-[(4-methylphenyl)methyl]-4-phenylpiperidine-4-carbonitrile
• 化学式: C₂₁H₂₃ClN₂
• 分子量: 338.88
• InChiKey: IPFWDVLVKLDFGG-NHCUHLMSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  cis-2-chloromethyl-1-(4-methylbenzyl)-4-phenylpiperidine-4-carbonitrile 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以75%的产率得到2-(4-methylbenzyl)-5-phenyl-2,7-diazabicyclo[3.3.1]nonane
  参考文献：
  名称：

  Synthesis of Stereodefined Piperidines from Aziridines and Their Transformation into Conformationally Constrained Amino Acids, Amino Alcohols and 2,7-Diazabicyclo[3.3.1]nonanes

  摘要：

  2-(2-Cyano-2-phenylethyl)azindines were converted into novel cis- and trans-2-chloromethyl-4-phenylpiperidine-4-carbonitriles via alkylation with 1-bromo-2-chloroethane followed by microwave-assisted 6-exo-tet cyclization and regiospecific ring opening The latter piperidines were used as eligible substrates for the synthesis of stereodefined 2-chloromethyl-, 2-hydroxymethyl-, and 2-carboxymethyl-4-phenylpiperidine-4-carboxylic acids, 2-hydroxymethyl-4-phenylpiperidine-4-carbonitriles, 3-hydroxy-5-phenylazepane-5-carbonitriles, and 5-phenyl-2,7-diazabicyclo[3 3 1]nonanes

  DOI：

  10.1021/jo101646u
• 作为产物：
  描述：

  2-(溴甲基)-1-[(4-甲基苯基)甲基]氮杂环丙烷 以 四氢呋喃 、 乙腈 为溶剂， 反应 0.5h， 生成 cis-2-chloromethyl-1-(4-methylbenzyl)-4-phenylpiperidine-4-carbonitrile
  参考文献：
  名称：

  Radical-mediated nitrile translocation as the key step in the stereoselective transformation of 2-(4-chloro-2-cyanobutyl)aziridines to methyl cis-(1-arylmethyl-4-phenylpiperidin-2-yl)acetates

  摘要：

  未活化的2-(4-氯-2-氰基-2-苯基丁基)氮杂环丁烷作为构建块，通过微波辅助的氮杂环丁烷到哌啶的环扩展进行立体选择性合成新型顺式-2-氰基甲基-4-苯基哌啶，随后经过中间双环亚胺自由基的初始形成及后续裂解，进行自由基诱导的氰基迁移。此外，这些2-(氰基甲基)哌啶被证明是制备甲基顺式-(1-芳基甲基-4-哌啶-2-基)乙酸酯的合格底物，该反应采用气态氯化氢在甲醇中进行Pinner反应。

  DOI：

  10.1039/c2ob07062f

文献信息

• Synthesis of Stereodefined Piperidines from Aziridines and Their Transformation into Conformationally Constrained Amino Acids, Amino Alcohols and 2,7-Diazabicyclo[3.3.1]nonanes
  作者：Karel Vervisch、Matthias D’hooghe、Karl W. Törnroos、Norbert De Kimpe

  DOI：10.1021/jo101646u

  日期：2010.11.19

  2-(2-Cyano-2-phenylethyl)azindines were converted into novel cis- and trans-2-chloromethyl-4-phenylpiperidine-4-carbonitriles via alkylation with 1-bromo-2-chloroethane followed by microwave-assisted 6-exo-tet cyclization and regiospecific ring opening The latter piperidines were used as eligible substrates for the synthesis of stereodefined 2-chloromethyl-, 2-hydroxymethyl-, and 2-carboxymethyl-4-phenylpiperidine-4-carboxylic acids, 2-hydroxymethyl-4-phenylpiperidine-4-carbonitriles, 3-hydroxy-5-phenylazepane-5-carbonitriles, and 5-phenyl-2,7-diazabicyclo[3 3 1]nonanes
• Radical-mediated nitrile translocation as the key step in the stereoselective transformation of 2-(4-chloro-2-cyanobutyl)aziridines to methyl cis-(1-arylmethyl-4-phenylpiperidin-2-yl)acetates
  作者：Karel Vervisch、Matthias D'hooghe、Karl W. Törnroos、Norbert De Kimpe

  DOI：10.1039/c2ob07062f

  日期：——

  Non-activated 2-(4-chloro-2-cyano-2-phenylbutyl)aziridines were used as building blocks for the stereoselective synthesis of novel cis-2-cyanomethyl-4-phenylpiperidines via a microwave-assisted aziridine to piperidine ring expansion followed by a radical-induced nitrile translocation through initial formation and subsequent cleavage of intermediate bicyclic iminyl radicals. Furthermore, these 2-(cyanomethyl)piperidines were shown to be eligible substrates for the preparation of methyl cis-(1-arylmethyl-4-piperidin-2-yl)acetates through a Pinner reaction using gaseous HCl in methanol.

  未活化的2-(4-氯-2-氰基-2-苯基丁基)氮杂环丁烷作为构建块，通过微波辅助的氮杂环丁烷到哌啶的环扩展进行立体选择性合成新型顺式-2-氰基甲基-4-苯基哌啶，随后经过中间双环亚胺自由基的初始形成及后续裂解，进行自由基诱导的氰基迁移。此外，这些2-(氰基甲基)哌啶被证明是制备甲基顺式-(1-芳基甲基-4-哌啶-2-基)乙酸酯的合格底物，该反应采用气态氯化氢在甲醇中进行Pinner反应。