1,4-difluoro-2-({[4-(trifluoromethyl)phenyl]thio}methyl)benzene | 886060-99-7

• 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: 1,4-difluoro-2-({[4-(trifluoromethyl)phenyl]thio}methyl)benzene
• 英文别名: 1,4-Difluoro-2-[[4-(trifluoromethyl)phenyl]sulfanylmethyl]benzene
• CAS: 886060-99-7
• 化学式: C₁₄H₉F₅S
• 分子量: 304.283
• InChiKey: VTXCUYOOTITLRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  25.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,4-difluoro-2-({[4-(trifluoromethyl)phenyl]thio}methyl)benzene 在 盐酸羟胺 、 potassium tert-butylate 、 双氧水 、 chloroamine-T 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 乙醇 、 水 、 溶剂黄146 、 二甲基亚砜 、 甲苯 为溶剂， 反应 27.25h， 生成 (3aR,5R,7aS)-5-(2,5-Difluoro-phenyl)-5-(4-trifluoromethyl-benzenesulfonyl)-octahydro-benzo[c]isoxazole
  参考文献：
  名称：

  Practical Asymmetric Synthesis of a γ-Secretase Inhibitor Exploiting Substrate-Controlled Intramolecular Nitrile Oxide−Olefin Cycloaddition

  摘要：

  A practical asymmetric synthesis of the gamma-secretase inhibitor (-)-1 is described. As the key transformation, a highly diastereoselective intramolecular nitrile oxide cycloaddition forms the hexahydrobenzisoxazole core of 3 in four operations. Other aspects of the route include a highly stereoselective reduction of an isoxazole to form a cis-gamma-amino alcohol, an efficient chemical resolution, a dianion cyclization to construct a sultam ring, and the alpha-alkylation of a sultam with excellent diastereoselectivity. In each instance, the relative stereochemistry was evolved by way of substrate-based induction with >= 96% ds. Kilogram quantities of the targeted drug candidate (-)-1 were obtained, without recourse to chromatography, by way of 10 isolated intermediates and in 13% overall yield.

  DOI：

  10.1021/jo060033i
• 作为产物：
  描述：

  4-(三氟甲基)苯硫酚 、 2,5-二氟苄溴 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以99%的产率得到1,4-difluoro-2-({[4-(trifluoromethyl)phenyl]thio}methyl)benzene
  参考文献：
  名称：

  Practical Asymmetric Synthesis of a γ-Secretase Inhibitor Exploiting Substrate-Controlled Intramolecular Nitrile Oxide−Olefin Cycloaddition

  摘要：

  A practical asymmetric synthesis of the gamma-secretase inhibitor (-)-1 is described. As the key transformation, a highly diastereoselective intramolecular nitrile oxide cycloaddition forms the hexahydrobenzisoxazole core of 3 in four operations. Other aspects of the route include a highly stereoselective reduction of an isoxazole to form a cis-gamma-amino alcohol, an efficient chemical resolution, a dianion cyclization to construct a sultam ring, and the alpha-alkylation of a sultam with excellent diastereoselectivity. In each instance, the relative stereochemistry was evolved by way of substrate-based induction with >= 96% ds. Kilogram quantities of the targeted drug candidate (-)-1 were obtained, without recourse to chromatography, by way of 10 isolated intermediates and in 13% overall yield.

  DOI：

  10.1021/jo060033i

文献信息

• Practical Asymmetric Synthesis of a γ-Secretase Inhibitor Exploiting Substrate-Controlled Intramolecular Nitrile Oxide−Olefin Cycloaddition
  作者：Jeremy P. Scott、Steven F. Oliver、Karel M. J. Brands、Sarah E. Brewer、Antony J. Davies、Andrew D. Gibb、David Hands、Stephen P. Keen、Faye J. Sheen、Robert A. Reamer、Robert D. Wilson、Ulf-H. Dolling

  DOI：10.1021/jo060033i

  日期：2006.4.1

  A practical asymmetric synthesis of the gamma-secretase inhibitor (-)-1 is described. As the key transformation, a highly diastereoselective intramolecular nitrile oxide cycloaddition forms the hexahydrobenzisoxazole core of 3 in four operations. Other aspects of the route include a highly stereoselective reduction of an isoxazole to form a cis-gamma-amino alcohol, an efficient chemical resolution, a dianion cyclization to construct a sultam ring, and the alpha-alkylation of a sultam with excellent diastereoselectivity. In each instance, the relative stereochemistry was evolved by way of substrate-based induction with >= 96% ds. Kilogram quantities of the targeted drug candidate (-)-1 were obtained, without recourse to chromatography, by way of 10 isolated intermediates and in 13% overall yield.