benzyl 1-(3-fluorophenyl)-4-hydroxy-7-methyl-2-oxo-1,8-diazaspiro[4.5]decane-8-carboxylate | 1222891-39-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: benzyl 1-(3-fluorophenyl)-4-hydroxy-7-methyl-2-oxo-1,8-diazaspiro[4.5]decane-8-carboxylate
• CAS: 1222891-39-5
• 化学式: C₂₃H₂₅FN₂O₄
• 分子量: 412.461
• InChiKey: JVIILOLMAFGYQM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl 1-(3-fluorophenyl)-4-hydroxy-7-methyl-2-oxo-1,8-diazaspiro[4.5]decane-8-carboxylate 在 吡啶 、 氯化亚砜 作用下， 反应 19.0h， 以61%的产率得到(5R,7S)-benzyl 1-(3-fluorophenyl)-7-methyl-2-oxo-1,8-diazaspiro[4.5]dec-3-ene-8-carboxylate
  参考文献：
  名称：

  Stereoselective Synthesis of Spiropiperidines as BACE-1 Aspartyl Protease Inhibitors via Late Stage N-Arylation of a 1,8-Diazaspiro[4.5]dec-3-en-2-one Pharmacophore

  摘要：

  A stereoselective synthesis of spiropiperidine compounds, exemplified by compound 1, was developed, which was based upon the late stage N-arylation of a 1,8-diazaspiro[4.5]dec-3-en-2-one pharmacophore. Previously, compound 1 was prepared in low overall yield from piperidinone 2 via the Strecker reaction. A new route was developed, which employed the stereospecific Corey-Link reaction of an enantiomerically pure trichloromethylcarbinol to give a template compound amenable to late stage N-arylation.

  DOI：

  10.1021/jo400016m
• 作为产物：
  描述：

  (S)-1-CBZ-2-甲基-4-哌啶酮 在 2,6-二甲基吡啶 、 盐酸 、 sodium tetrahydroborate 、 sodium ethanolate 、 溶剂黄146 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 61.75h， 生成 benzyl 1-(3-fluorophenyl)-4-hydroxy-7-methyl-2-oxo-1,8-diazaspiro[4.5]decane-8-carboxylate
  参考文献：
  名称：

  Stereoselective Synthesis of Spiropiperidines as BACE-1 Aspartyl Protease Inhibitors via Late Stage N-Arylation of a 1,8-Diazaspiro[4.5]dec-3-en-2-one Pharmacophore

  摘要：

  A stereoselective synthesis of spiropiperidine compounds, exemplified by compound 1, was developed, which was based upon the late stage N-arylation of a 1,8-diazaspiro[4.5]dec-3-en-2-one pharmacophore. Previously, compound 1 was prepared in low overall yield from piperidinone 2 via the Strecker reaction. A new route was developed, which employed the stereospecific Corey-Link reaction of an enantiomerically pure trichloromethylcarbinol to give a template compound amenable to late stage N-arylation.

  DOI：

  10.1021/jo400016m

文献信息

• Stereoselective Synthesis of Spiropiperidines as BACE-1 Aspartyl Protease Inhibitors via Late Stage <i>N</i>-Arylation of a 1,8-Diazaspiro[4.5]dec-3-en-2-one Pharmacophore
  作者：Che-Wah Lee、Ricardo Lira、Jason Dutra、Kevin Ogilvie、Brian T. O’Neill、Michael Brodney、Christopher Helal、Joseph Young、Erik Lachapelle、Subas Sakya、John C. Murray

  DOI：10.1021/jo400016m

  日期：2013.3.15

  A stereoselective synthesis of spiropiperidine compounds, exemplified by compound 1, was developed, which was based upon the late stage N-arylation of a 1,8-diazaspiro[4.5]dec-3-en-2-one pharmacophore. Previously, compound 1 was prepared in low overall yield from piperidinone 2 via the Strecker reaction. A new route was developed, which employed the stereospecific Corey-Link reaction of an enantiomerically pure trichloromethylcarbinol to give a template compound amenable to late stage N-arylation.