8-(2-(benzyloxy)-ethyl)-8-azabicyclo[3.2.1]octan-3-one | 1428580-80-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: 8-(2-(benzyloxy)-ethyl)-8-azabicyclo[3.2.1]octan-3-one
• CAS: 1428580-80-6
• 化学式: C₁₆H₂₁NO₂
• 分子量: 259.348
• InChiKey: TVELLZVUUCGNSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  29.54
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  8-(2-(benzyloxy)-ethyl)-8-azabicyclo[3.2.1]octan-3-one 在 potassium tert-butylate 、 三甲基碘化亚砜 、 二异丁基氢化铝 、 三乙胺 作用下， 以 四氢呋喃 、 2-甲基四氢呋喃 、 甲苯 、 叔丁醇 为溶剂， 反应 28.0h， 生成 3-(8-(2-(benzyloxy)ethyl)-8-azabicyclo[3.2.1]octan-3-yl)-2,2-diphenylpropanenitrile
  参考文献：
  名称：

  Development of Synthetic Routes, via a Tropinone Intermediate, to a Long-Acting Muscarinic Antagonist for the Treatment of Respiratory Disease

  摘要：

  This contribution describes the development of two synthetic routes to an investigational muscarinic antagonist for the treatment of chronic obstructive pulmonary disease. The first route used a starting material which was in plentiful supply within the GSK network and was used to make material for early clinical trials and safety assessment studies. Further investigations identified a second, potential long-term manufacturing route from commercially available building blocks, using substrate control to install the two stereocentres with excellent selectivity. A key step was a substrate-directed epoxide reduction which also gave rise to a minor byproduct through a skeletal rearrangement of the tropane ring. A deuterium-labeling experiment was carried out, which shed light on the origin of the byproduct, and also guided the improvement of reaction conditions.

  DOI：

  10.1021/op3002933
• 作为产物：
  描述：

  氯化苄 在 盐酸 、 sodium hydride 作用下， 以 四氢呋喃 、 水 、 mineral oil 为溶剂， 反应 2.0h， 生成 8-(2-(benzyloxy)-ethyl)-8-azabicyclo[3.2.1]octan-3-one
  参考文献：
  名称：

  Development of Synthetic Routes, via a Tropinone Intermediate, to a Long-Acting Muscarinic Antagonist for the Treatment of Respiratory Disease

  摘要：

  This contribution describes the development of two synthetic routes to an investigational muscarinic antagonist for the treatment of chronic obstructive pulmonary disease. The first route used a starting material which was in plentiful supply within the GSK network and was used to make material for early clinical trials and safety assessment studies. Further investigations identified a second, potential long-term manufacturing route from commercially available building blocks, using substrate control to install the two stereocentres with excellent selectivity. A key step was a substrate-directed epoxide reduction which also gave rise to a minor byproduct through a skeletal rearrangement of the tropane ring. A deuterium-labeling experiment was carried out, which shed light on the origin of the byproduct, and also guided the improvement of reaction conditions.

  DOI：

  10.1021/op3002933