(2S)-2-(2-isopropyl)-5-hydroxy-2-phenylpentanenitrile | 350795-08-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S)-2-(2-isopropyl)-5-hydroxy-2-phenylpentanenitrile
• 英文别名: (S)-(+)-4-cyano-5-methyl-4-phenylhexanol；(2S)-5-hydroxy-2-phenyl-2-propan-2-ylpentanenitrile
• CAS: 350795-08-3
• 化学式: C₁₄H₁₉NO
• 分子量: 217.311
• InChiKey: ONRWLQMTZBJKMQ-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  44
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2S)-2-(2-isopropyl)-5-hydroxy-2-phenylpentanenitrile 在 三乙酰氧基硼氢化钠 、 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 、 溶剂黄146 、 1,2-二氯乙烷 为溶剂， 反应 3.0h， 生成 (S)-noremopamil
  参考文献：
  名称：

  Practical Synthesis of Chiral Emopamil Left Hand as a Bioactive Motif

  摘要：

  An asymmetric synthesis of (2S)-2-(2-isopropyl)-5-hydroxy-2-phenylpentanenitrile (emopamil left hand, 2) has been completed by use of the MAD (methyl aluminum bis(4-methyl-2,6-di-tert-butylphenoxide)-induced rearrangement of a chiral epoxyalcohol as the key reaction. The stereochemistry of the chiral quaternary center was confirmed by transformation of 2 to (S)-noremopamil. This method requires minimal purification procedures and affords high chemical and optical yields. Acid-catalyzed isomerization of an allylaldehyde and retro-aldol type racemization at the quaternary carbon of a nitrile-alcohol were encountered.

  DOI：

  10.1021/jo020166d
• 作为产物：
  描述：

  (+/-)-methyl 4-cyano-5-methyl-4-phenylhexanoate 在 lithium aluminium tetrahydride 、 Pseudomonas sp. immobilized lipase 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.7h， 生成 (2S)-2-(2-isopropyl)-5-hydroxy-2-phenylpentanenitrile
  参考文献：
  名称：

  Enantioselective synthesis of (2S)-5-{4-[2-(4-fluorophenoxy)ethyl]piperazin-1-yl}-2-isopropyl-2-phenyl-pentanenitrile dihydrochloride (E2050) using enzyme-catalyzed kinetic resolution

  摘要：

  Immobilized lipase (Pseudomonas sp.)-catalyzed transesterification of (RS)-4-cyano-4-isopropyl-4-phenyl-1-butanol 4 in vinyl acetate gave (S)-4-cyano-4-isopropyl-4-phenyl-1-butyl acetate 3a with high enantiomeric excess values and conversions (95-97% ee, 30-47%, E = 90-93), leaving the enantiomerically pure (R)-alcohol 4 (>99% ee) unreacted. As 3a can be efficiently converted to E2050, use of the immobilized lipase should provide an economical route for large-scale synthesis of E2050. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(02)00364-6

文献信息

• Practical Synthesis of Chiral Emopamil Left Hand as a Bioactive Motif
  作者：Teiji Kimura、Noboru Yamamoto、Yuichi Suzuki、Koki Kawano、Yoshihiko Norimine、Koichi Ito、Satoshi Nagato、Yoichi Iimura、Masahiro Yonaga

  DOI：10.1021/jo020166d

  日期：2002.8.1

  An asymmetric synthesis of (2S)-2-(2-isopropyl)-5-hydroxy-2-phenylpentanenitrile (emopamil left hand, 2) has been completed by use of the MAD (methyl aluminum bis(4-methyl-2,6-di-tert-butylphenoxide)-induced rearrangement of a chiral epoxyalcohol as the key reaction. The stereochemistry of the chiral quaternary center was confirmed by transformation of 2 to (S)-noremopamil. This method requires minimal purification procedures and affords high chemical and optical yields. Acid-catalyzed isomerization of an allylaldehyde and retro-aldol type racemization at the quaternary carbon of a nitrile-alcohol were encountered.
• Enantioselective synthesis of (2S)-5-{4-[2-(4-fluorophenoxy)ethyl]piperazin-1-yl}-2-isopropyl-2-phenyl-pentanenitrile dihydrochloride (E2050) using enzyme-catalyzed kinetic resolution
  作者：Yoshihiko Norimine、Noboru Yamamoto、Yuichi Suzuki、Teiji Kimura、Koki Kawano、Koichi Ito、Satoshi Nagato、Yoichi Iimura、Masahiro Yonaga

  DOI：10.1016/s0957-4166(02)00364-6

  日期：2002.8

  Immobilized lipase (Pseudomonas sp.)-catalyzed transesterification of (RS)-4-cyano-4-isopropyl-4-phenyl-1-butanol 4 in vinyl acetate gave (S)-4-cyano-4-isopropyl-4-phenyl-1-butyl acetate 3a with high enantiomeric excess values and conversions (95-97% ee, 30-47%, E = 90-93), leaving the enantiomerically pure (R)-alcohol 4 (>99% ee) unreacted. As 3a can be efficiently converted to E2050, use of the immobilized lipase should provide an economical route for large-scale synthesis of E2050. (C) 2002 Elsevier Science Ltd. All rights reserved.