(S)-5-methyl-3-nitromethyl hexanoic acid ethyl ester | 911822-96-3

• 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: (S)-5-methyl-3-nitromethyl hexanoic acid ethyl ester
• 英文别名: (S) ethyl 5-methyl-3-nitromethyl-hexanoate；(S)-ethyl 5-methyl-3-nitromethyl-hexanoate；(S)-5-methyl-3-nitromethyl-hexanoic acid ethyl ester；ethyl (3S)-5-methyl-3-(nitromethyl)hexanoate
• CAS: 911822-96-3
• 化学式: C₁₀H₁₉NO₄
• 分子量: 217.265
• InChiKey: LOHHVAYLSGONPS-VIFPVBQESA-N

物化性质

• 沸点：
  297.0±23.0 °C(Predicted)
• 密度：
  1.031±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-5-methyl-3-nitromethyl hexanoic acid ethyl ester 在 palladium 10% on activated carbon 氢气 、 盐酸 、 水 、 Dowex 50W 作用下， 以 溶剂黄146 为溶剂， 25.0 ℃ 、506.66 kPa 条件下， 反应 5.4h， 生成 普瑞巴林
  参考文献：
  名称：

  WO2006/110783

  摘要：

  公开号：
• 作为产物：
  描述：

  (S)-ethyl 2-carboethoxy-3-(nitromethyl)-5-methylhexanoate 在 水 、 sodium chloride 作用下， 以 二甲基亚砜 为溶剂， 反应 5.0h， 生成 (S)-5-methyl-3-nitromethyl hexanoic acid ethyl ester
  参考文献：
  名称：

  WO2006/110783

  摘要：

  公开号：

文献信息

• PROCESS FOR THE PREPARATION OF PREGABALIN
  申请人：HIKAL LIMITED

  公开号：US20150344919A1

  公开（公告）日：2015-12-03

  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 pa (V) to racemic 3-cyano-5-methyl-hexanoic acid or salt thereof of formula (VI) with a genetically modified nitrilase enzyme (Nit pt 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.

  本发明提供了一种改进的制备化合物(I)的方法，包括以下步骤：式(I)，(a)在适当溶剂中，将式(II)异戊醛和式(III)烷基氰乙酸酯在弱酸和弱碱盐或弱碱的存在下反应，得到式(IV)的2-氰基-5-甲基-己-2-烯酸烷基酯；(b)将式(IV)的2-氰基-5-甲基-己-2-烯酸烷基酯与适当的氰化物源在水中或有机溶剂中或二者的混合物中反应，得到式(V)的2-异丁基琥珀酰腈；(c)通过在水中或有机溶剂中或二者的混合物中的单步反应，将式(II)异戊醛和式(III)烷基氰乙酸酯在适当的氰化物源的存在下反应，可选地获得式(V)的2-异丁基琥珀酰腈；(d)通过在水中或适当的pH和温度下，用一种基因改造的腈酶酶(Nit pt 9N_56_2)将式(V)的2-异丁基琥珀酰腈转化为外消旋3-氰基-5-甲基-己酸或其盐的式(VI)；(e)通过在适当溶剂或其混合物中，在碱的存在下，用醇(R3OH)和酸性催化剂或烷基卤化物(R3X)处理，将式(VI)的外消旋3-氰基-5-甲基-己酸或其盐转化为式(VII)的外消旋烷基3-氰基-5-甲基-己酸酯；(f)通过在水或有机溶剂或其混合物中，通过酶选择性立体选择性水解，从式(VII)的外消旋烷基3-氰基-5-甲基-己酸酯获得(S)-烷基3-氰基-5-甲基-己酸酯的式(VIII)和(R)-3-氰基-5-甲基-己酸或其盐的式(X)；(g)通过在有机溶剂或其混合物中，在碱的存在下，将不需要的(R)-3-氰基-5-甲基-己酸或其盐的式(X)或富集的(R)-3-氰基-5-甲基-己酸或其盐的式(X)外消旋化，可选地获得式(VII)的化合物；(h)通过在水或其他有机溶剂或其混合物中，在适当的氢化催化剂的存在下，将(S)-烷基3-氰基-5-甲基-己酸酯转化为式(I)的前列酸，首先用适当的碱或碱土金属碱水解酯基，然后在一个锅中进行氢化。
• [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）。
• 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）。
• PROCESS FOR THE STEREOSELECTIVE ENZYMATIC HYDROLYSIS OF 5-METHYL-3-NITROMETHYL-HEXANOIC ACID ESTER
  申请人：Albert Martin

  公开号：US20110165636A1

  公开（公告）日：2011-07-07

  The present invention relates to processes for the preparation of 5-methyl-3-nitromethyl-hexanoic acid ester and its salts. Also disclosed are processes for the preparation of 5-methyl-3-nitromethyl-hexanoic acid salt and a process for the preparation of 3-(aminomethyl)-5-methylhexanoic acid. (S)-5-Methyl-3-nitromethyl-hexanoic acid or (R)-5-methyl-3-nitromethyl-hexanoic acid in enantioenriched form or enantiopure form as well as salts thereof, (S)-5-methyl-3-nitromethyl-hexanoic acid ester or (R)-5-methyl-3-nitromethyl-hexanoic acid ester in enantioenriched form or enantiopure form and a compound, namely Formula (XIII), in racemic form, enantioenriched form or enantiopure form are also disclosed.

  本发明涉及制备5-甲基-3-硝基甲基己酸酯及其盐的过程。还公开了制备5-甲基-3-硝基甲基己酸盐和3-(氨甲基)-5-甲基己酸的过程。本发明还公开了(S)-5-甲基-3-硝基甲基己酸或(R)-5-甲基-3-硝基甲基己酸在对映富集形式或对映纯形式以及其盐，(S)-5-甲基-3-硝基甲基己酸酯或(R)-5-甲基-3-硝基甲基己酸酯在对映富集形式或对映纯形式以及一种化合物，即式(XIII)，在外消旋形式、对映富集形式或对映纯形式。
• Process for the stereoselective enzymatic hydrolysis of 5-methyl-3-nitromethyl-hexanoic acid ester
  申请人：Albert Martin

  公开号：US08546112B2

  公开（公告）日：2013-10-01

  The present invention relates to processes for the preparation of 5-methyl-3-nitromethyl-hexanoic acid ester and its salts. Also disclosed are processes for the preparation of 5-methyl-3-nitromethyl-hexanoic acid salt and a process for the preparation of 3-(aminomethyl)-5-methylhexanoic acid. (S)-5-Methyl-3-nitromethyl-hexanoic acid or (R)-5-methyl-3-nitromethyl-hexanoic acid in enantioenriched form or enantiopure form as well as salts thereof, (S)-5-methyl-3-nitromethyl-hexanoic acid ester or (R)-5-methyl-3-nitromethyl-hexanoic acid ester in enantioenriched form or enantiopure form and a compound, namely Formula (XIII), in racemic form, enantioenriched form or enantiopure form are also disclosed.

  本发明涉及制备5-甲基-3-硝基甲基己酸酯及其盐的过程。还揭示了制备5-甲基-3-硝基甲基己酸盐和3-(氨甲基)-5-甲基己酸的过程。本发明还揭示了(S)-5-甲基-3-硝基甲基己酸或(R)-5-甲基-3-硝基甲基己酸的对映富集形式或对映纯形式及其盐，(S)-5-甲基-3-硝基甲基己酸酯或(R)-5-甲基-3-硝基甲基己酸酯的对映富集形式或对映纯形式，以及一种化合物，即公式(XIII)，其为外消旋体、对映富集形式或对映纯形式。