(S)-(1-benzyl-2,5-dioxo-pyrrolidin-3-yl)carbamic acid benzyl ester | 124166-11-6

• 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: (S)-(1-benzyl-2,5-dioxo-pyrrolidin-3-yl)carbamic acid benzyl ester
• 英文别名: (3S)-1-benzyl-3-benzyloxycarbonylaminopyrrolidine-2,5-dione；benzyl N-[(3S)-1-benzyl-2,5-dioxopyrrolidin-3-yl]carbamate
• CAS: 124166-11-6
• 化学式: C₁₉H₁₈N₂O₄
• 分子量: 338.363
• InChiKey: DRPFKGKSRKPPCG-INIZCTEOSA-N

物化性质

• 沸点：
  597.1±50.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-(1-benzyl-2,5-dioxo-pyrrolidin-3-yl)carbamic acid benzyl ester 在 palladium on carbon 氢气 作用下， 以 乙醇 为溶剂， 反应 34.0h， 以91%的产率得到(3S)-3-氨基-1-苄基吡咯烷-2,5-二酮
  参考文献：
  名称：

  Process for producing optically active 1H-3-aminopyrrolidine and derivatives thereof

  摘要：

  公开号：

  EP1188744B1
• 作为产物：
  描述：

  N-benzyloxycarbonyl-D,L-asparagine n-butyl ester 在 sodium hydroxide 、 Alcalase 2.4L from Bacillus sp 、 sodium hydride 、 sodium chloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 phosphate buffer 为溶剂， 反应 94.33h， 生成 (S)-(1-benzyl-2,5-dioxo-pyrrolidin-3-yl)carbamic acid benzyl ester
  参考文献：
  名称：

  Chemo-enzymatic preparation of chiral 3-aminopyrrolidine derivatives

  摘要：

  A new simple method for the enantioselective enzymatic hydrolysis of N-protected D-asparagine esters suitable for the use on the preparative scale is presented. Due to major obstacles observed under conventional reaction conditions-racemization of the retained ester and a strong enzyme inactivation-a comparatively low pH together with an organic co-solvent had to be employed. Under these conditions, nearly all tested proteases demonstrated good activity and excellent enantioselectivity giving access to the corresponding D-esters and L-asparagines in high optical purities (>95% ee) and good chemical yields (>40%). From the unnatural D-asparagine derivative, sequential cyclization, selective deprotection and reduction yielded efficiently benzyl protected (R)-3-aminopyrrolidine, a homo-chiral building block utilized in numerous drug candidates. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2003.10.118

文献信息

• Process for producing 1H-3-aminopyrrolidine and derivatives thereof
  申请人：Mitsubishi Chemical Corporation

  公开号：US20020042523A1

  公开（公告）日：2002-04-11

  A process for producing 1H-3-aminopyrrolidine and derivatives thereof is disclosed. The process is especially useful for producing optically active 1H-3-aminopyrrolidine and derivatives thereof and in this case comprises reacting an optically active amino-protected aspartic anhydride represented by the formula (1) with a primary amine represented by the formula R′NH 2 , subjecting the reaction product to cyclodehydration to obtain an optically active 1 -aralkyl-3-(protected amino)pyrrolidine-2,5-dione compound represented by the formula (2), subsequently eliminating the protective group from the 3-position amino group of the compound represented by the formula (2) to obtain an optically active 1-aralkyl-3-aminopyrrolidine-2,5-dione compound represented by the formula (3), reducing the carbonyl groups of the compound represented by the formula (3) to obtain either an optically active 1-aralkyl-3-aminopyrrolidine compound represented by the formula (4) or a salt thereof with a protonic acid, and then subjecting the compound represented by the formula (4) or the salt thereof to hydrogenolysis to obtain an optically active 1H-3-aminopyrrolidine or a protonic acid salt thereof.

  公开了一种生产1H-3-氨基吡咯烷及其衍生物的方法。该方法特别适用于生产光学活性的1H-3-氨基吡咯烷及其衍生物，其中包括将公式（1）表示的光学活性氨基保护的天冬氨酸酐与公式R'NH2表示的一级胺反应，将反应产物经过环化脱水作用得到公式（2）表示的光学活性1-芳基甲基-3-(保护氨基)吡咯烷-2,5-二酮化合物，随后消除公式（2）所表示的化合物中3位氨基基团的保护基，得到公式（3）表示的光学活性1-芳基甲基-3-氨基吡咯烷-2,5-二酮化合物，将公式（3）所表示的化合物的羰基基团还原，得到公式（4）表示的光学活性1-芳基甲基-3-氨基吡咯烷化合物或其与质子酸的盐，然后将公式（4）所表示的化合物或其盐进行氢解，得到光学活性的1H-3-氨基吡咯烷或其质子酸盐。
• Process for producing 1H-3-aminopyrrolidine and derivatives thereof
  申请人：MITSUBISHI CHEMICAL CORPORATION

  公开号：EP1188744A1

  公开（公告）日：2002-03-20

  A process for producing 1H-3-aminopyrrolidine and derivatives thereof is disclosed. The process is especially useful for producing optically active 1H-3-aminopyrrolidine and derivatives thereof and in this case comprises reacting an optically active amino-protected aspartic anhydride represented by the formula (1) with a primary amine represented by the formula R'NH2, subjecting the reaction product to cyclodehydration to obtain an optically active 1-aralkyl-3-(protected amino)pyrrolidine-2,5-dione compound represented by the formula (2), subsequently eliminating the protective group from the 3-position amino group of the compound represented by the formula (2) to obtain an optically active 1-aralkyl-3-aminopyrrolidine-2,5-dione compound represented by the formula (3), reducing the carbonyl groups of the compound represented by the formula (3) to obtain either an optically active 1-aralkyl-3-aminopyrrolidine compound represented by the formula (4) or a salt thereof with a protonic acid, and then subjecting the compound represented by the formula (4) or the salt thereof to hydrogenolysis to obtain an optically active 1H-3-aminopyrrolidine or a protonic acid salt thereof.

  本发明公开了一种生产 1H-3-氨基吡咯烷及其衍生物的工艺。该工艺特别适用于生产具有光学活性的 1H-3-氨基吡咯烷及其衍生物，在这种情况下，该工艺包括将式（1）所代表的具有光学活性的氨基保护天冬氨酸酐与式 R'NH2 所代表的伯胺反应，使反应产物进行环脱水反应，得到式（2）所代表的具有光学活性的 1-烷基-3-（保护氨基）吡咯烷-2,5-二酮化合物、随后从式（2）代表的化合物的 3 位氨基上消除保护基团，得到式（3）代表的光学活性 1-烷基-3-氨基吡咯烷-2,5-二酮化合物、用质子酸还原式（3）所代表化合物的羰基，以获得光学活性的 1-烷基-3-氨基吡咯烷化合物（式（4）所代表）或其盐，然后将式（4）所代表化合物或其盐进行氢解，以获得光学活性的 1H-3- 氨基吡咯烷或其质子酸盐。
• Process for producing optically active 1H-3-aminopyrrolidine and derivatives thereof
  申请人：MITSUBISHI CHEMICAL CORPORATION

  公开号：EP1188744B1

  公开（公告）日：2005-11-02
• US6531594B2
  申请人：——

  公开号：US6531594B2

  公开（公告）日：2003-03-11
• Handy access to chiral N,N′-disubstituted 3-aminopyrrolidines.
  作者：Jacques Maddaluno、Aline Corruble、Valéric Leroux、Gérard Plé、Pierre Duhamel

  DOI：10.1016/s0957-4166(00)82081-9

  日期：1992.10

  A new and rapid synthesis of (S)-3-aminopyrrolidines 7 is proposed from N-protected (S)-Asparagine. Basic cyclization of methyl N-Z-(S)-Asparaginate 1 followed by one-pot N-benzylation directly leads to (S)-aminosuccinimide 3 which, after cleavage of the Z-protecting group, is converted to corresponding imines and readily reduced to disubstituted chiral 3-aminopyrrolidines 7. Almost no racemization (less-than-or-equal-to 5%) of the original amino-acid asymmetric center may be observed.