(R) ethyl 5-methyl-3-bromo-hexanoate | 1166864-51-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (R) ethyl 5-methyl-3-bromo-hexanoate
• 英文别名: (+/-) ethyl 5-methyl-3-bromo-hexanoate；Ethyl 5-methyl-3-bromo-hexanoate；ethyl 3-bromo-5-methylhexanoate
• CAS: 1166864-51-2
• 化学式: C₉H₁₇BrO₂
• 分子量: 237.137
• InChiKey: IBMYSFUJRKIQAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  12
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  硝基甲烷 、 (R) ethyl 5-methyl-3-bromo-hexanoate 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以96%的产率得到5-甲基-3-(硝基甲基)己酸乙酯
  参考文献：
  名称：

  PROCESS TO PREGABALIN

  摘要：

  本发明涉及一种新的方法，用于制备外消旋的pregabalin（1）或其单一对映体（S）-（+）-3-（氨甲基）-5-甲基-己酸（2）。

  公开号：

  US20100324139A1
• 作为产物：
  描述：

  ethyl 3-hydroxy-5-methyl-hexanoate 在 溴 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 以70%的产率得到(R) ethyl 5-methyl-3-bromo-hexanoate
  参考文献：
  名称：

  PROCESS TO PREGABALIN

  摘要：

  本发明涉及一种新的方法，用于制备外消旋的pregabalin（1）或其单一对映体（S）-（+）-3-（氨甲基）-5-甲基-己酸（2）。

  公开号：

  US20100324139A1

文献信息

• [EN] PROCESSES TO PREGABALIN<br/>[FR] PROCÉDÉS DE PRÉPARATION DE LA PRÉGABALINE
  申请人：GENERICS UK LTD

  公开号：WO2009081208A1

  公开（公告）日：2009-07-02

  The present invention relates to a novel method for the preparation of racemic pregabalin (1) or a single enantiomer thereof, (S)-(+)-3-(aminomethyl)-5-methyl-hexanoic acid (2).

  本发明涉及一种新颖的方法，用于制备外消旋的pregabalin（1）或其单一对映体（S）-（+）-3-（氨甲基）-5-甲基-己酸（2）。
• PROCESSES TO PREGABALIN
  申请人：Generics (UK) Limited

  公开号：EP2222630A1

  公开（公告）日：2010-09-01
• [EN] A PROCESS FOR THE PREPARATION OF PREGABALIN<br/>[FR] PROCÉDÉ DE PRÉPARATION DE PRÉGABALINE
  申请人：HIKAL LTD

  公开号：WO2014072785A2

  公开（公告）日：2014-05-15

  The present invention provides an improved process for the preparation of a compound of formula (I), which comprises the steps of: formula (I), (a) reacting isovaleraldehyde of formula (II) and alkyl cyanoacetate of formula (III) optionally in presence of salts of weak acid and weak base or weak base in a suitable solvent to get 2-cyano-5- methyl-hex-2-enoic acid alkyl ester of formula (IV); (b) reacting 2-cyano-5-methyl-hex-2-enoic acid alkyl ester of formula (IV) with a suitable cyanide source in water or in an organic solvent or mixture thereof to get 2-isobutylsuccinonitrile of formula (V); (c) obtaining optionally 2-isobutylsuccinonitrile of formula (V) by reacting isovaleraldehyde of formula (II) and alkyl cyanoacetate of formula (III) in presence of suitable cyanide source in water or in an organic solvent or mixture thereof in single step; (d) converting 2-isobutylsuccinonitrile of formula (V) to racemic 3-cyano-5-methyl-hexanoic acid or salt thereof of formula (VI) with a genetically modified nitrilase enzyme (Nit 9N_56_2) in water or optionally with an organic co-solvent at appropriate pH and temperature; (e) converting racemic 3-cyano-5-methyl-hexanoic acid or salt thereof of formula (VI) to racemic alkyl 3-cyano-5-methyl-hexanoate of formula (VII) by treatment with alcohol (R3OH) and acidic catalyst or alkyl halide (R3X) in presence of a base in a suitable solvent or a mixture of solvents thereof;.(f) obtaining (S)-alkyl 3 -cyano-5 -methyl -hexanoate of formula (VIII) and (R)-3-cyano-5-methyl- hexanoic acid or salt thereof of formula (X) by enzymatic enantioselective hydrolysis in water or organic solvent or a mixture thereof from racemic alkyl 3-cyano-5-methyl-hexanoate of formula (VII);.(g) obtaining optionally the compound of formula (VII) by racemizing unwanted (R)-3-cyano-5- methyl-hexanoic acid or salt thereof of formula (X) or substantially enriched (R)-3 -cyano-5 - methyl-hexanoic acid salt thereof of formula (X) in presence of a base in organic solvent or a mixture thereof; (h) converting (S)-alkyl 3-cyano-5-methyl-hexanoate of formula (VIII) to pregabalin of formula (I) by hydrolyzing ester group with suitable alkali or alkaline earth metal base followed by hydrogenation optionally in one pot in a solvent selected from water or other organic solvents or a mixture thereof in presence of a suitable hydrogenation catalyst.
• PROCESS TO PREGABALIN
  申请人：Gaitonde Abhay

  公开号：US20100324139A1

  公开（公告）日：2010-12-23

  The present invention relates to a novel method for the preparation of racemic pregabalin (1) or a single enantiomer thereof, (S)-(+)-3-(aminomethyl)-5-methyl-hexanoic acid (2).

  本发明涉及一种新的方法，用于制备外消旋的pregabalin（1）或其单一对映体（S）-（+）-3-（氨甲基）-5-甲基-己酸（2）。