tert-butyl 4-(2-hydroxyethyl)-4-(pyrrolidin-1-yl)-piperidine-1-carboxylate | 1323999-44-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-(2-hydroxyethyl)-4-(pyrrolidin-1-yl)-piperidine-1-carboxylate
• 英文别名: Tert-butyl 4-(2-hydroxyethyl)-4-(pyrrolidin-1-YL)piperidine-1-carboxylate；tert-butyl 4-(2-hydroxyethyl)-4-pyrrolidin-1-ylpiperidine-1-carboxylate
• CAS: 1323999-44-5
• 化学式: C₁₆H₃₀N₂O₃
• 分子量: 298.426
• InChiKey: HVPDIJBVEGQTAS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  53
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 红铝 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 以9.25 kg的产率得到tert-butyl 4-(2-hydroxyethyl)-4-(pyrrolidin-1-yl)-piperidine-1-carboxylate
  参考文献：
  名称：

  Pilot Plant Preparation of tert-Butyl-4-(2-hydroxyethyl)-4-(pyrrolidin-1-yl)-piperidine-1-carboxylate, An Intermediate of Novel Antiarteriosclerotics, Via a Safe, Scalable Reformatsky-Type Reaction

  摘要：

  Reported here is a safe, scalable process via a Reformatsky-type reaction of iminium salt (4) followed by Red-Al reduction giving tert-butyl-4-(2-hydroxyethyl)-4-(pyrrolidin-1-yl)-piperidine-1-carboxylate (6), an intermediate of novel antiarteriosclerotics (1). The key points of this safe process are the use of trifluoroacetic acid (TFA) for the iminium salt formation, vigorous stirring for the Reformatsky reaction, and slow addition of methyl bromoacetate. Pilot manufacturing on the 500 L scale was achieved.

  DOI：

  10.1021/op2001723

文献信息

• Practical Synthesis of Ethyl 1-(<i>tert</i>-Butoxycarbonyl)-4-(1-pyrrolidinyl)-4-piperidineacetate, an Intermediate of a Novel Antiarteriosclerotic, Utilizing Aza-Michael Addition Promoted by LiBr
  作者：Akira Iida、Naohiro Onodera、Tatsuro Yasukata

  DOI：10.1246/cl.2012.1703

  日期：2012.12.5

  The aza-Michael addition of pyrrolidine to β,β-dialkylated unsaturated ester 6 utilizing LiBr proceeded smoothly to give the inaccessible ethyl 1-(tert-butoxycarbonyl)-4-(1-pyrrolidinyl)-4-piperidineacetate (7), which is an intermediate of novel antiarteriosclerotic 1.

  利用 LiBr 将吡咯烷与β,β-二烷基不饱和酯 6 进行杂-迈克尔加成反应，顺利地生成了不可获取的 1-（叔丁氧羰基）-4-（1-吡咯烷基）-4-哌啶乙酸乙酯（7），它是新型抗动脉硬化药 1 的中间体。
• Pilot Plant Preparation of <i>tert-</i>Butyl-4-(2-hydroxyethyl)-4-(pyrrolidin-1-yl)-piperidine-1-carboxylate, An Intermediate of Novel Antiarteriosclerotics, Via a Safe, Scalable Reformatsky-Type Reaction
  作者：Hiroshi Osato、Motonari Osaki、Takao Oyama、Youhei Takagi、Takemasa Hida、Koichi Nishi、Mikio Kabaki

  DOI：10.1021/op2001723

  日期：2011.11.18

  Reported here is a safe, scalable process via a Reformatsky-type reaction of iminium salt (4) followed by Red-Al reduction giving tert-butyl-4-(2-hydroxyethyl)-4-(pyrrolidin-1-yl)-piperidine-1-carboxylate (6), an intermediate of novel antiarteriosclerotics (1). The key points of this safe process are the use of trifluoroacetic acid (TFA) for the iminium salt formation, vigorous stirring for the Reformatsky reaction, and slow addition of methyl bromoacetate. Pilot manufacturing on the 500 L scale was achieved.