3-[(S)-1-(methyl-[(S)-1-phenylethyl]amino)ethyl]phenol | 1017234-23-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 3-[(S)-1-(methyl-[(S)-1-phenylethyl]amino)ethyl]phenol
• 英文别名: 3-[(S)-1-(methyl-[(S)-1-phenylethyl]amino) ethyl]phenol；3-[(1S)-1-[methyl-[(1S)-1-phenylethyl]amino]ethyl]phenol
• CAS: 1017234-23-9
• 化学式: C₁₇H₂₁NO
• 分子量: 255.36
• InChiKey: RBTONRBPOFOGTK-KBPBESRZSA-N

物化性质

• 熔点：
  99-100 °C(Solv: ethyl acetate (141-78-6); ligroine (8032-32-4))
• 沸点：
  357.2±22.0 °C(Predicted)
• 密度：
  1.065±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-[(S)-1-(methyl-[(S)-1-phenylethyl]amino)ethyl]phenol 在 甲酸 、 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 、 水 为溶剂， 20.0~70.0 ℃ 、517.12 kPa 条件下， 反应 19.0h， 生成 3-(1-(S)-(N,N-二甲基氨基)乙基)苯酚
  参考文献：
  名称：

  General Strategy for Large-Scale Synthesis of (+)-Rivastigmine and (+)-NPS R-568

  摘要：

  An economically viable strategy for the total synthesis of (+)-rivastigmine and (+)-NPS R-568 has been reported. The strategy involves regioselective hydrogenation of diastereomerically pure bis amine to realize the desired alpha-methyl chiral substituted benzyl amine. The route is economical, scalable, and versatile enough to be adapted to similar classes of compounds.

  DOI：

  10.1080/00397911.2010.527425
• 作为产物：
  描述：

  在 sodium tetrahydroborate 、 甲酸 作用下， 以 乙醇 、 水 、 乙酸乙酯 为溶剂， 反应 13.0h， 生成 3-[(S)-1-(methyl-[(S)-1-phenylethyl]amino)ethyl]phenol
  参考文献：
  名称：

  General Strategy for Large-Scale Synthesis of (+)-Rivastigmine and (+)-NPS R-568

  摘要：

  An economically viable strategy for the total synthesis of (+)-rivastigmine and (+)-NPS R-568 has been reported. The strategy involves regioselective hydrogenation of diastereomerically pure bis amine to realize the desired alpha-methyl chiral substituted benzyl amine. The route is economical, scalable, and versatile enough to be adapted to similar classes of compounds.

  DOI：

  10.1080/00397911.2010.527425

文献信息

• PREPARATION METHOD FOR RIVASTIGMINE, INTERMEDIATES THEREOF, AND PREPARATION METHOD FOR SAID INTERMEDIATES
  申请人：Zhang Fuli

  公开号：US20140073809A1

  公开（公告）日：2014-03-13

  The present invention provides the preparation method for (S)-3-(1-(dimethylamino)ethyl)phenyl ethyl(methyl)carbamate (formula X compound), the preparation methods for its intermediates (S)-1-(3-methoxyphenyl)-N,N-dimethyl-N—((S)-1-phenylethyl)ethanaminium (formula VI compound), (S)-1-(3-hydroxyphenyl)-N,N-dimethyl-N—((S)-1-phenylethyl)ethanaminium (formula VIII compound) and (S)-1-(3-(ethyl(methyl)carbamoyloxy)phenyl)-N,N-dimethyl-N—((S)-1-phenylethyl)ethanaminium (formula IX compound), as well as the method for using above mentioned formula IX compound to prepare rivastigmine which can be used for the treatment of Alzheimer's disease. The preparation method for rivastigmine has a reasonable synthetic design with convenient source of raw materials and high total yield, and the product resulted has high chemical and optical purity, which makes it easy for large-scale. industrial production.

  本发明提供了(S)-3-(1-(二甲基氨基)乙基)苯基乙基(甲基)氨基甲酸酯（化合物X的结构）的制备方法，以及其中间体(S)-1-(3-甲氧基苯基)-N,N-二甲基-N-((S)-1-苯乙基)乙胺盐（化合物VI的结构）、(S)-1-(3-羟基苯基)-N,N-二甲基-N-((S)-1-苯乙基)乙胺盐（化合物VIII的结构）和(S)-1-(3-(乙基(甲基)氨基甲酰氧基)苯基)-N,N-二甲基-N-((S)-1-苯乙基)乙胺盐（化合物IX的结构）的制备方法，以及利用上述化合物IX制备利伐替林的方法，利伐替林可用于治疗阿尔茨海默病。利伐替林的制备方法具有合理的合成设计，原料来源便利，总产率高，所得产品具有高化学和光学纯度，便于大规模工业生产。
• Preparation method for rivastigmine, intermediates thereof, and preparation method for said intermediates
  申请人：Zhang Fuli

  公开号：US09353049B2

  公开（公告）日：2016-05-31

  The present invention provides a preparation method for (S)-3-(1-(dimethylamino)ethyl)phenyl ethyl(methyl)carbamate, preparation methods for intermediates (S)-1-(3-methoxyphenyl)-N,N-dimethyl-N—((S)-1-phenylethyl)ethanaminium, (S)-1-(3-hydroxyphenyl)-N,N-dimethyl-N—((S)-1-phenylethyl)ethanaminium and (S)-1-(3-(ethyl(methyl)carbamoyloxy)phenyl)-N,N-dimethyl-N—((S)-1-phenylethyl)ethanaminium, as well as a method for using (S)-1-(3-(ethyl(methyl)carbamoyloxy)phenyl)-N,N-dimethyl-N—((S)-1-phenylethyl)ethanaminium to prepare rivastigmine which can be used for the treatment of Alzheimer's disease.

  本发明提供了(S)-3-(1-(二甲氨基)乙基)苯基乙基(甲基)氨基甲酸酯的制备方法，以及中间体(S)-1-(3-甲氧基苯基)-N,N-二甲基-N-((S)-1-苯乙基)乙胺，(S)-1-(3-羟基苯基)-N,N-二甲基-N-((S)-1-苯乙基)乙胺和(S)-1-(3-(乙基(甲基)氨基甲酰氧)苯基)-N,N-二甲基-N-((S)-1-苯乙基)乙胺的制备方法，以及使用(S)-1-(3-(乙基(甲基)氨基甲酰氧)苯基)-N,N-二甲基-N-((S)-1-苯乙基)乙胺制备治疗阿尔茨海默病的利巴韦林的方法。
• PREPATATION METHOD OF RIVASTIGMINE, ITS INTERMEDIATES AND PREPARATION METHOD OF THE INTERMEDIATES
  申请人：Zhang Fuli

  公开号：US20100286437A1

  公开（公告）日：2010-11-11

  The present invention provides N-methylethylcarbamino-3-[(S)-1-(methyl-[(S)-1-phenylethyl]amino)ethyl]phenyl ester represented by formula (II) and its preparation method. The present invention also provides (S)-1-(3-methoxyphenyl)-N-methyl-N—[(S)-1-phenylethyl]ethylamine and 3-[(S)-1-(methyl-[(S)-1-phenylethyl]amino)ethyl]phenol as intermediates of the compound represented by formula (II), and the use of the compound represented by formula (II) for preparing rivastigmine used for treating Alzheimer disease.

  本发明提供了公式（II）所表示的N-甲基乙基氨基-3-[(S)-1-(甲基-[(S)-1-苯乙基]氨基)乙基]苯酯及其制备方法。本发明还提供了(S)-1-(3-甲氧基苯基)-N-甲基-N-[(S)-1-苯乙基]乙胺和3-[(S)-1-(甲基-[(S)-1-苯乙基]氨基)乙基]苯酚作为公式（II）所表示的化合物的中间体，并且提供了利用公式（II）所表示的化合物制备用于治疗阿尔茨海默病的利巴韦林的方法。
• Novel Convenient Synthesis of Rivastigmine
  作者：Meng Hu、Fu-Li Zhang、Mei-Hua Xie

  DOI：10.1080/00397910802531948

  日期：2009.4.7

  A novel and convenient synthesis of rivastigmine has been reported. This procedure provides high yield and excellent enantiomeric excess (100% ee) starting from the diastereromerically pure (S)-1-(3-methoxyphenyl)-N-[(S)-1-phenylethyl] ethanamine.
• PREPARATION METHOD OF RIVASTIGMINE, ITS INTERMEDIATES AND PREPARATION METHOD OF THE INTERMEDIATES
  申请人：Shanghai Institute of Pharmaceutical Industry

  公开号：EP2233465B1

  公开（公告）日：2017-06-28