3(R,S)-bromo-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydropyridine hydrobromide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3(R,S)-bromo-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydropyridine hydrobromide
• 英文别名: 3(R,S)-Bromo-1methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydropyridine Hydrobromide；3-bromo-1-methyl-4-(2,4,6-trimethoxyphenyl)-3,6-dihydro-2H-pyridine;hydrobromide
• 化学式: BrH*C₁₅H₂₀BrNO₃
• 分子量: 423.145
• InChiKey: ITPBYEUERJAVHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.38
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  30.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3(R,S)-bromo-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydropyridine hydrobromide 以 水 为溶剂， 生成 3(R,S)-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydro-pyridine
  参考文献：
  名称：

  Method for producing (−)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-piperidine

  摘要：

  本发明公开了一种制备(−)顺式-3-羟基-1-甲基-4-(2,4,6-三甲氧基苯基)-哌啶的方法，其特征在于将1-甲基哌啶-4-酮转化为氢溴酸盐，随后与溴反应转化为3(R,S)-溴-1-甲基-4-氧代吡啶-氢溴酸盐，并与1,3,5-三甲氧基苯基反应形成3(R,S)-溴-1-甲基-4-(2,4,6-三甲氧基苯基)-1,2,3,6-四氢吡啶-氢溴酸盐。通过将反应溶液搅拌到有机溶剂中，首先以固体形式分离得到3(R,S)-溴-1-甲基-4-(2,4,6-三甲氧基苯基)-1,2,3,6-四氢吡啶-氢溴酸盐，随后通过搅拌将产物与水混合转化为3(R,S)-羟基-1-甲基-4-(2,4,6-三甲氧基苯基)-1,2,3,6-四氢吡啶。因此制备的产物经催化氢化成为一个外消旋的3,4-顺式醇，随后通过手性辅助试剂从外消旋的3,4-顺式醇中分离得到对映纯的(−)顺式-3-羟基-1-甲基-4-(2,4,6-三甲氧基苯基)-哌啶。

  公开号：

  US06225473B1
• 作为产物：
  描述：

  N-甲基-4-哌啶酮 、 1,3,5-三甲氧基苯 、 甲基叔丁基醚 在 氢溴酸 、 溴 作用下， 以 二氯甲烷 、 溶剂黄146 为溶剂， 生成 3(R,S)-bromo-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydropyridine hydrobromide
  参考文献：
  名称：

  Method for producing (−)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-piperidine

  摘要：

  本发明公开了一种制备(−)顺式-3-羟基-1-甲基-4-(2,4,6-三甲氧基苯基)-哌啶的方法，其特征在于将1-甲基哌啶-4-酮转化为氢溴酸盐，随后与溴反应转化为3(R,S)-溴-1-甲基-4-氧代吡啶-氢溴酸盐，并与1,3,5-三甲氧基苯基反应形成3(R,S)-溴-1-甲基-4-(2,4,6-三甲氧基苯基)-1,2,3,6-四氢吡啶-氢溴酸盐。通过将反应溶液搅拌到有机溶剂中，首先以固体形式分离得到3(R,S)-溴-1-甲基-4-(2,4,6-三甲氧基苯基)-1,2,3,6-四氢吡啶-氢溴酸盐，随后通过搅拌将产物与水混合转化为3(R,S)-羟基-1-甲基-4-(2,4,6-三甲氧基苯基)-1,2,3,6-四氢吡啶。因此制备的产物经催化氢化成为一个外消旋的3,4-顺式醇，随后通过手性辅助试剂从外消旋的3,4-顺式醇中分离得到对映纯的(−)顺式-3-羟基-1-甲基-4-(2,4,6-三甲氧基苯基)-哌啶。

  公开号：

  US06225473B1

文献信息

• Process for the preparation of (-)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)piperidine
  申请人：Aventis Pharma Deutschland GmbH.

  公开号：US20010051728A1

  公开（公告）日：2001-12-13

  Disclosed is a method for producing (−)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-piperidine characterized in that 1-methyl-piperidine-4-one is converted into hydrobromide, subsequently transformed with bromine into 3(R,S)-bromine-1-methyl-4-oxo-piperidine-hydrobromide and reacted with 1,3,5-trimethoxybenzol to form 3(R,S)-bromine-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydro-pyridine-hydrobromide. By stirring the reaction solution into an organic solvent, 3(R,S)-bromine-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydro-pyridine-hydrobomide is initially isolated as a solid and subsequently the product is mixed with water and converted into 3(R,S)-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydro-pyridine by means of stirring. The product thus prepared is catalytically hydrogenated into a racemic 3,4-cis-alcohol and subsequently, enantiomerically pure (−)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-piperidine is obtained by separation of racemic mixtures with chiral auxiliary reagents from racemic 3,4-cis alcohol.

  本发明公开了一种制备(−)顺式-3-羟基-1-甲基-4-(2,4,6-三甲氧基苯基)-哌啶的方法，其特征在于将1-甲基哌啶-4-酮转化为氢溴酸盐，随后与溴反应形成3(R,S)-溴-1-甲基-4-氧代哌啶-氢溴酸盐，然后与1,3,5-三甲氧基苯基反应形成3(R,S)-溴-1-甲基-4-(2,4,6-三甲氧基苯基)-1,2,3,6-四氢-吡啶-氢溴酸盐。通过将反应溶液搅拌到有机溶剂中，最初以固体形式分离出3(R,S)-溴-1-甲基-4-(2,4,6-三甲氧基苯基)-1,2,3,6-四氢-吡啶-氢溴酸盐，随后通过搅拌将产物与水混合转化为3(R,S)-羟基-1-甲基-4-(2,4,6-三甲氧基苯基)-1,2,3,6-四氢-吡啶。因此制备的产物经过催化氢化后形成一个外消旋的3,4-顺式醇，随后通过手性助剂试剂从外消旋的3,4-顺式醇中分离出对映纯的(−)顺式-3-羟基-1-甲基-4-(2,4,6-三甲氧基苯基)-哌啶。
• US06437136B1
  申请人：——

  公开号：——

  公开（公告）日：——
• Method for producing (−)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-piperidine
  申请人：Aventis Pharma Deutschland GmbH

  公开号：US06225473B1

  公开（公告）日：2001-05-01

  Disclosed is a method for producing (−)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-piperidine characterised in that 1-methyl-piperidine-4-one is converted into hydrobromide, subsequently transformed with bromine into 3(R,S)-bromine-1-methyl-4-oxo-pyridine-hydrobromide and reacted with 1,3,5-trimethoxyphenyl to form 3(R,S)-bromine-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydro-pyridine-hydrobromide. By stirring the reaction solution into an organic solvent, 3(R,S)-bromine-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydro-pyridine-hydrobromide is initially isolated as a solid and subsequently the product is mixed with water and converted into 3(R,S)-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydro-pyridine by means of stirring. The product thus prepared is catalytically hydrogenated into a racemic 3,4-cis-alcahol and subsequently, enantiomerically pure (−)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-piperidine is obtained by separation of recemic mixtures with chiral auxiliary reagents from recemic 3,4-cis alcohol.

  本发明公开了一种制备(−)顺式-3-羟基-1-甲基-4-(2,4,6-三甲氧基苯基)-哌啶的方法，其特征在于将1-甲基哌啶-4-酮转化为氢溴酸盐，随后与溴反应转化为3(R,S)-溴-1-甲基-4-氧代吡啶-氢溴酸盐，并与1,3,5-三甲氧基苯基反应形成3(R,S)-溴-1-甲基-4-(2,4,6-三甲氧基苯基)-1,2,3,6-四氢吡啶-氢溴酸盐。通过将反应溶液搅拌到有机溶剂中，首先以固体形式分离得到3(R,S)-溴-1-甲基-4-(2,4,6-三甲氧基苯基)-1,2,3,6-四氢吡啶-氢溴酸盐，随后通过搅拌将产物与水混合转化为3(R,S)-羟基-1-甲基-4-(2,4,6-三甲氧基苯基)-1,2,3,6-四氢吡啶。因此制备的产物经催化氢化成为一个外消旋的3,4-顺式醇，随后通过手性辅助试剂从外消旋的3,4-顺式醇中分离得到对映纯的(−)顺式-3-羟基-1-甲基-4-(2,4,6-三甲氧基苯基)-哌啶。