(2S,4S)-methyl 1-[4,4-bis(3-methyl-2-thienyl)-3-buten-1-yl]-4-fluoropyrrolidine-2-carboxylate | 1157865-28-5

• 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: (2S,4S)-methyl 1-[4,4-bis(3-methyl-2-thienyl)-3-buten-1-yl]-4-fluoropyrrolidine-2-carboxylate
• 英文别名: methyl (2S,4S)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-4-fluoropyrrolidine-2-carboxylate；methyl (2S,4S)-1-[4,4-bis(3-methylthiophen-2-yl)but-3-enyl]-4-fluoropyrrolidine-2-carboxylate
• CAS: 1157865-28-5
• 化学式: C₂₀H₂₄FNO₂S₂
• 分子量: 393.546
• InChiKey: LRUQICDMYOUEPF-RDJZCZTQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  86
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,4S)-methyl 1-[4,4-bis(3-methyl-2-thienyl)-3-buten-1-yl]-4-fluoropyrrolidine-2-carboxylate 在 乙醇 、 sodium hydroxide 、 盐酸 、 水 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以87%的产率得到(2S,4S)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-4-fluoropyrrolidine-2-carboxylic acid hydrochloride
  参考文献：
  名称：

  Synthesis and biological evaluation of 4-fluoroproline and 4-fluoropyrrolidine-2-acetic acid derivatives as new GABA uptake inhibitors

  摘要：

  Preparation for the N-alkylated derivatives of enantiomerically pure (2S)-4-fluoroproline and (2S)-4-fluoropyrrolidine-2-acetic acid is described. The final compounds were evaluated as potential GAT-1 uptake inhibitors via cultured cell lines expressing mouse GAT-1. Compared with their corresponding 4-hydroxy compounds, these derivatives exhibited slight improvement on their inhibitory potency, but still much weaker than their corresponding compounds with no substituents at the C-4 of the pyrrolidine moiety, with the most potent affinity being about 1/15 fold as that of Tiagabine. The drastic decrease of their affinity may arise from sharp reduction of their basicity due to strong inductive effect of the 4-fluorine. However the configuration of the C-4 linking fluorine did not have much influence on their affinity for GAT-1. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.08.010
• 作为产物：
  描述：

  methyl (2S,4R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-4-hydroxylpyrrolidine-2-carboxylate 在 全氟丁基磺酰氟 、 N,N-二异丙基乙胺 、 四丁基二氟三苯硅酸铵 作用下， 以 甲苯 为溶剂， 反应 24.0h， 以84%的产率得到(2S,4S)-methyl 1-[4,4-bis(3-methyl-2-thienyl)-3-buten-1-yl]-4-fluoropyrrolidine-2-carboxylate
  参考文献：
  名称：

  A Highly Efficient Conversion of Primary or Secondary Alcohols into Fluorides with n-Perfluorobutanesulfonyl Fluoride-Tetrabutylammonium Triphenyldifluorosilicate

  摘要：

  在温和的条件下，全氟-1-丁磺酰氟（PBSF）和四丁基三苯基氟硅酸铵（TBAT）组合对伯醇和仲醇进行直接氟化反应，可获得高产率的相应氟化物。在这种组合下，消除副反应的效果明显减弱，手性仲醇在反应中心也不易发生缩合反应。

  DOI：

  10.1055/s-0028-1087931