ethyl (3S,4S)-3-nitromethyl-4,5-isopropylidenepentanoate | 156636-67-8

• 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: ethyl (3S,4S)-3-nitromethyl-4,5-isopropylidenepentanoate
• 英文别名: (S)-ethyl-3-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)-4-nitrobutanoate；ethyl (S)-3-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)-4-nitrobutanoate；(S)-Ethyl 3-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)-4-nitrobutanoate；ethyl (3S)-3-[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]-4-nitrobutanoate
• CAS: 156636-67-8
• 化学式: C₁₁H₁₉NO₆
• 分子量: 261.275
• InChiKey: AUDIVQVJJMELHM-DTWKUNHWSA-N

物化性质

• 沸点：
  354.1±27.0 °C(Predicted)
• 密度：
  1.150±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  90.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl (3S,4S)-3-nitromethyl-4,5-isopropylidenepentanoate 在 palladium(II) hydroxide/carbon 甲酸铵 作用下， 以 甲醇 为溶剂， 以85%的产率得到(S)-4-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)pyrrolidin-2-one
  参考文献：
  名称：

  Process for the enantioselective preparation of pregabalin

  摘要：

  本发明提供了一种新的对映选择性过程，用于制备（S）-普瑞巴林，或制备药物可接受的加酸盐，包括：将手性化合物的二氧兰环进行酸水解，得到通式（II）的化合物；将化合物（II）氧化得到通式（III）的化合物，并将化合物（III）转化为通式（IV）的化合物；将化合物（IV）进行碱性水解得到通式（V）的化合物，然后还原得到对映纯的S-普瑞巴林。本发明还提供了参与该过程的新手性中间体。

  公开号：

  EP2017273A1
• 作为产物：
  描述：

  硝基甲烷 、 3-<(4'S)-2',2'-dimethyl-1',3'-dioxolan-4'-yl>prop-2-enoic acid ethyl ester 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以83%的产率得到ethyl (3S,4S)-3-nitromethyl-4,5-isopropylidenepentanoate
  参考文献：
  名称：

  Process for the enantioselective preparation of pregabalin

  摘要：

  本发明提供了一种新的对映选择性过程，用于制备（S）-普瑞巴林，或制备药物可接受的加酸盐，包括：将手性化合物的二氧兰环进行酸水解，得到通式（II）的化合物；将化合物（II）氧化得到通式（III）的化合物，并将化合物（III）转化为通式（IV）的化合物；将化合物（IV）进行碱性水解得到通式（V）的化合物，然后还原得到对映纯的S-普瑞巴林。本发明还提供了参与该过程的新手性中间体。

  公开号：

  EP2017273A1

文献信息

• Diastereoselective Michael Addition of Nitromethane to Enoates Derived From (<i>R</i>)-Glyceraldehyde Acetonide
  作者：Vera L. Patrocinio、Paulo R. R. Costa、Carlos R. D. Correia

  DOI：10.1055/s-1994-25504

  日期：——

  The Michael addition of nitromethane to enoates derived from glyceraldehyde acetonide leads to syn-adducts 3 with high diastereoselectivity (de 76-90 %). The stereochemistry of the new stereogenic center was determined by transforming the Michael adduct 3b into lactone 6a.

  将硝基甲烷与乙醛缩丙酮衍生的烯酸盐进行迈克尔加成，可生成具有高非对映选择性（de 76-90%）的合成加成物 3。通过将迈克尔加成物 3b 转化为内酯 6a，确定了新立体中心的立体化学结构。
• PROCESS FOR THE ENANTIOSELECTIVE PREPARATION OF PREGABALIN
  申请人：Ortuno Rosa M.

  公开号：US20100197939A1

  公开（公告）日：2010-08-05

  The invention provides a new enantioselective process for the preparation of (S)-pregabalin, or a pharmaceutical acceptable addition acid salt comprising: acid hydrolysis of the dioxolan ring of a chiral compound of general formula (I) to obtain compound of general formula (II); oxidation of compound (II) to obtain a compound of general formula (III) and transforming compound (III) into compound of general formula (IV); subjecting compound (IV) to basic hydrolysis to obtain a compound of general formula (V) which is reduced to obtain enantiomerically pure S-pregabalin. The invention also provides new chiral intermediates involved in the process.

  本发明提供了一种新的对映选择性工艺，用于制备（S）-普瑞巴林，或其药物可接受的酸盐，包括：对手性化合物（I）的二氧六环环的酸水解，以获得通式（II）的化合物；将化合物（II）氧化，以获得通式（III）的化合物，并将化合物（III）转化为通式（IV）的化合物；将化合物（IV）进行碱性水解，以获得通式（V）的化合物，然后还原化合物（V）以获得对映纯的S-普瑞巴林。本发明还提供了涉及该过程的新手性中间体。
• Stereoselective and efficient synthesis of (S)-pregabalin from d-mannitol
  作者：Sandra Izquierdo、Jordi Aguilera、Helmut H. Buschmann、Mónica García、Antoni Torrens、Rosa M. Ortuño

  DOI：10.1016/j.tetasy.2008.03.005

  日期：2008.4

  A straightforward synthesis of (S)-pregabalin in 28% overall yield starting from D-mannitol acetonide, as a primary source of chirality, is presented. The process is suitable for large-scale synthesis and involves simple and high-yielding chemical transformations as well as low-cost commercially available reagents. (c) 2008 Elsevier Ltd. All rights reserved.
• [EN] PROCESS FOR THE ENANTIOSELECTIVE PREPARATION OF PREGABALIN<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION ÉNANTIOSÉLECTIVE DE LA PRÉGABALINE
  申请人：ESTEVE LABOR DR

  公开号：WO2009010554A1

  公开（公告）日：2009-01-22

  The invention provides a new enantioselective process for the preparation of (S) -pregabalin, or a pharmaceutical acceptable addition acid salt comprising: acid hydrolysis of the dioxolan ring of a chiral compound of general formula (I) to obtain compound of general formula (II); oxidation of compound (II) to obtain a compound of general formula (III) and transforming compound (III) into compound of general formula (IV); subjecting compound (IV) to basic hydrolysis to obtain a compound of general formula (V) which is reduced to obtain enantiomerically pure S-pregabalin. The invention also provides new chiral intermediates involved in the process.
• Process for the enantioselective preparation of pregabalin
  申请人：Laboratorios del Dr. Esteve S.A.

  公开号：EP2017273A1

  公开（公告）日：2009-01-21

  The invention provides a new enantioselective process for the preparation of (S)-pregabalin, or a pharmaceutical acceptable addition acid salt comprising: acid hydrolysis of the dioxolan ring of a chiral compound of general formula (I) to obtain compound of general formula (II); oxidation of compound (II) to obtain a compound of general formula (III) and transforming compound (III) into compound of general formula (IV); subjecting compound (IV) to basic hydrolysis to obtain a compound of general formula (V) which is reduced to obtain enantiomerically pure S-pregabalin. The invention also provides new chiral intermediates involved in the process.

  本发明提供了一种新的对映选择性过程，用于制备（S）-普瑞巴林，或制备药物可接受的加酸盐，包括：将手性化合物的二氧兰环进行酸水解，得到通式（II）的化合物；将化合物（II）氧化得到通式（III）的化合物，并将化合物（III）转化为通式（IV）的化合物；将化合物（IV）进行碱性水解得到通式（V）的化合物，然后还原得到对映纯的S-普瑞巴林。本发明还提供了参与该过程的新手性中间体。