N-(2-fluoro-5-trifluoromethylbenzyl)cinchonidinium bromide | 1225330-66-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 金鸡纳生物碱
• 英文名称: N-(2-fluoro-5-trifluoromethylbenzyl)cinchonidinium bromide
• CAS: 1225330-66-4
• 化学式: Br*C₂₇H₂₇F₄N₂O
• 分子量: 551.422
• InChiKey: QLEWGXYGVALJHX-BAKFXFHVSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  3.04
• 重原子数：
  35.0
• 可旋转键数：
  5.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  33.12
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为产物：
  描述：

  辛可尼丁 、 2-氟-5-(三氟甲基)溴苄 以 甲苯 为溶剂， 以96%的产率得到N-(2-fluoro-5-trifluoromethylbenzyl)cinchonidinium bromide
  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