2-(3-(2,5-difluorophenyl)-3-{[4-(trifluoromethyl)phenyl]sulfonyl}hex-5-en-1-yl)-1,3-dioxolane | 886060-98-6

• 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: 2-(3-(2,5-difluorophenyl)-3-{[4-(trifluoromethyl)phenyl]sulfonyl}hex-5-en-1-yl)-1,3-dioxolane
• 英文别名: 2-[3-(2,5-Difluorophenyl)-3-[4-(trifluoromethyl)phenyl]sulfonylhex-5-enyl]-1,3-dioxolane
• CAS: 886060-98-6
• 化学式: C₂₂H₂₁F₅O₄S
• 分子量: 476.464
• InChiKey: BSUUXEGVKHELIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  61
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-(3-(2,5-difluorophenyl)-3-{[4-(trifluoromethyl)phenyl]sulfonyl}hex-5-en-1-yl)-1,3-dioxolane 在 盐酸羟胺 、 chloroamine-T 作用下， 以 乙醇 、 水 为溶剂， 反应 4.0h， 生成 cis-5-(2,5-difluorophenyl)-5-{[4-(trifluoromethyl)phenyl]sulfonyl}-3,3a,4,5,6,7-hexahydro-2,1-benzisoxazole
  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：

  2-(2-溴乙基)-1,3-二恶烷 在 potassium tert-butylate 作用下， 以 二甲基亚砜 为溶剂， 反应 1.75h， 生成 2-(3-(2,5-difluorophenyl)-3-{[4-(trifluoromethyl)phenyl]sulfonyl}hex-5-en-1-yl)-1,3-dioxolane
  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.