methyl (1R,2S)-1-(((E)-benzylidene)amino)-2-vinylcyclopropane-1-carboxylate | 1239881-07-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (1R,2S)-1-(((E)-benzylidene)amino)-2-vinylcyclopropane-1-carboxylate
• CAS: 1239881-07-2
• 化学式: C₁₄H₁₅NO₂
• 分子量: 229.279
• InChiKey: YJNPHLNYUCNOGR-LHVWTWQCSA-N

物化性质

• 沸点：
  318.3±42.0 °C(predicted)
• 密度：
  1.07±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.22
• 重原子数：
  17.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  38.66
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  1,4-二溴-2-丁烯 、 Methyl (E)-N-benzylideneglycinate 在 N-[2,5-bis(trifluoromethyl)benzyl]cinchonidinium bromide 、 水 、 sodium hydroxide 作用下， 以 甲苯 为溶剂， 反应 20.5h， 生成 、 methyl (1R,2S)-1-(((E)-benzylidene)amino)-2-vinylcyclopropane-1-carboxylate
  参考文献：
  名称：

  Enantioselective Synthesis of (1R,2S)-1-Amino-2-vinylcyclopropanecarboxylic Acid Ethyl Ester (Vinyl-ACCA-OEt) by Asymmetric Phase-Transfer Catalyzed Cyclopropanation of (E)-N-Phenylmethyleneglycine Ethyl Ester

  摘要：

  A concise asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid ethyl ester, a key intermediate in the preparation of many hepatitis C virus inhibitors, is described. Stereoselective cyclopropanation of (E)-N-phenylmethyleneglycine ethyl ester was effected by treatment with trans-1,4-dibromo-2-butene in the presence of a catalytic amount of a chiral phase-transfer catalyst. Microscale high-throughput experimentation techniques were successfully used to identify a cinchonidine-derived catalyst that provided (1R,2S)-1-(E)-N-phenylmethylene-amino-2-vinylcyclopropanecarboxylic acid ethyl ester in up to 84% cc. This was translated to a lab scale process to attain 78% yield and 77.4% cc. Chiral purity upgrade and isolation of the ester was accomplished via preparatory supercritical fluid chromatography followed by crystallization of the ester as its tosylate salt. The improved synthesis described herein represents a potentially more economical preparation of this valuable intermediate.

  DOI：

  10.1021/op100070d

文献信息

• METHOD FOR PRODUCING OPTICALLY ACTIVE 1-AMINO-2-VINYLCYCLOPROPANECARBOXYLIC ACID ESTER
  申请人：Aikawa Toshiaki

  公开号：US20120130116A1

  公开（公告）日：2012-05-24

  1-Amino-2-vinylcyclopropanecarboxylic acid ester, which is useful as a synthetic intermediate of pharmaceuticals, can be produced by a process of producing 1-amino-2-vinylcyclopropanecarboxylic acid ester represented by formula (4): including a step of hydrolysis of an optically active 1-N-(arylmethylene)amino-2-vinylcyclopropanecarboxylic acid ester represented by formula (3): which is obtained by reacting an N-(arylmethylene)glycine ester represented by formula (1): with a compound represented by formula (2): in the presence of a base and an optically active quaternary ammonium salt.

  1-氨基-2-乙烯基环丙烷羧酸酯是一种用作制药合成中间体的化合物，可以通过以下步骤制备：首先，将化合物（2）与代表式（1）的N-(芳基亚甲基)甘氨酸酯在碱和手性季铵盐的存在下反应，得到代表式（3）的手性1-N-(芳基亚甲基)氨基-2-乙烯基环丙烷羧酸酯；然后，对该化合物进行水解反应，得到代表式（4）的1-氨基-2-乙烯基环丙烷羧酸酯，该化合物可用作制药合成中间体。
• QUATERNARY AMMONIUM SALT
  申请人：Aikawa Toshiaki

  公开号：US20130296552A1

  公开（公告）日：2013-11-07

  A quaternary ammonium salt represented by formula ( 5 ) (wherein R 1 represents an alkyl group having 1 to 4 carbon atoms, R 2 represents an alkyl group having 1 to 10 carbon atoms, R 3 represents an alkyl group having 1 to 10 carbon atoms that is optionally substituted with one or more phenyl groups; or a phenyl group that optionally has one or more groups selected from the group consisting of alkyl groups having 1 to 10 carbon atoms and a trifluoromethyl group, R 4 represents an alkyl group having 1 to 4 carbon atoms, R 5 represents an alkyl group having 1 to 10 carbon atoms, C* represents an asymmetric carbon atom, and X − represents a halide ion) can be used as a catalyst having good stability under basic conditions.

  式(5)所表示的季铵盐，其中R1代表1至4个碳原子的烷基，R2代表1至10个碳原子的烷基，R3代表1至10个碳原子的烷基，可选地取代一个或多个苯基；或一个苯基，可选地具有来自由1至10个碳原子的烷基和三氟甲基组成的群中选择的一个或多个基团，R4代表1至4个碳原子的烷基，R5代表1至10个碳原子的烷基，C*代表一个不对称的碳原子，X-代表卤素离子，可用作在碱性条件下稳定性良好的催化剂。
• US8742162B2
  申请人：——

  公开号：US8742162B2

  公开（公告）日：2014-06-03
• US9259723B2
  申请人：——

  公开号：US9259723B2

  公开（公告）日：2016-02-16
• Enantioselective Synthesis of (1<i>R</i>,2<i>S</i>)-1-Amino-2-vinylcyclopropanecarboxylic Acid Ethyl Ester (Vinyl-ACCA-OEt) by Asymmetric Phase-Transfer Catalyzed Cyclopropanation of (<i>E</i>)-<i>N</i>-Phenylmethyleneglycine Ethyl Ester
  作者：Kevin M. Belyk、Bangping Xiang、Paul G. Bulger、William R. Leonard、Jaume Balsells、Jingjun Yin、Cheng-yi Chen

  DOI：10.1021/op100070d

  日期：2010.5.21

  A concise asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid ethyl ester, a key intermediate in the preparation of many hepatitis C virus inhibitors, is described. Stereoselective cyclopropanation of (E)-N-phenylmethyleneglycine ethyl ester was effected by treatment with trans-1,4-dibromo-2-butene in the presence of a catalytic amount of a chiral phase-transfer catalyst. Microscale high-throughput experimentation techniques were successfully used to identify a cinchonidine-derived catalyst that provided (1R,2S)-1-(E)-N-phenylmethylene-amino-2-vinylcyclopropanecarboxylic acid ethyl ester in up to 84% cc. This was translated to a lab scale process to attain 78% yield and 77.4% cc. Chiral purity upgrade and isolation of the ester was accomplished via preparatory supercritical fluid chromatography followed by crystallization of the ester as its tosylate salt. The improved synthesis described herein represents a potentially more economical preparation of this valuable intermediate.