(3R)-1-azabicyclo[2.2.2]oct-3-yl 4-nitrophenyl carbonate | 1243274-81-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3R)-1-azabicyclo[2.2.2]oct-3-yl 4-nitrophenyl carbonate
• 英文别名: [(3R)-1-azabicyclo[2.2.2]octan-3-yl] (4-nitrophenyl) carbonate
• CAS: 1243274-81-8
• 化学式: C₁₄H₁₆N₂O₅
• 分子量: 292.291
• InChiKey: IPSWQNYZUPFBSZ-ZDUSSCGKSA-N

物化性质

• 沸点：
  441.1±45.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  84.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3R)-1-azabicyclo[2.2.2]oct-3-yl 4-nitrophenyl carbonate 、 (S)-1-苯基-1,2,3,4-四氢异喹啉 以 N,N-二甲基甲酰胺 为溶剂， 生成 索非那新
  参考文献：
  名称：

  [EN] A NEW METHOD FOR THE PREPARATION OF SOLIFENACIN AND NEW INTERMEDIATE THEREOF
  [FR] NOUVEAU PROCÉDÉ DE PRÉPARATION DE LA SOLIFÉNACINE ET NOUVEL INTERMÉDIAIRE DANS SA PRÉPARATION

  摘要：

  一种通过将quinuclidin-3-ol和双(芳基)碳酸酯反应以形成式(IVa)的(3R)-1-azabicyclo[2.2.2]辛-3-基4-芳基碳酸酯来制备索利那新的方法；并在惰性气氛中处理式(IVa)的(3R)-1-azabicyclo[2.2.2]辛-3-基4-芳基碳酸酯，与(1S)-1-苯基-1,2,3,4-四氢异喹啉反应，形成转化为其药用可接受盐的索利那新碱。该发明还提供了新化合物(3R)-1-azabicyclo[2.2.2]辛-3-基4-芳基碳酸酯，用作制备索利那新碱的中间体及其制备方法。

  公开号：

  WO2010103529A1
• 作为产物：
  描述：

  二(对硝基苯)碳酸酯 、 (R)-(-)-3-奎宁醇 以 N,N-二甲基甲酰胺 为溶剂， 生成 (3R)-1-azabicyclo[2.2.2]oct-3-yl 4-nitrophenyl carbonate
  参考文献：
  名称：

  [EN] A NEW METHOD FOR THE PREPARATION OF SOLIFENACIN AND NEW INTERMEDIATE THEREOF
  [FR] NOUVEAU PROCÉDÉ DE PRÉPARATION DE LA SOLIFÉNACINE ET NOUVEL INTERMÉDIAIRE DANS SA PRÉPARATION

  摘要：

  一种通过将quinuclidin-3-ol和双(芳基)碳酸酯反应以形成式(IVa)的(3R)-1-azabicyclo[2.2.2]辛-3-基4-芳基碳酸酯来制备索利那新的方法；并在惰性气氛中处理式(IVa)的(3R)-1-azabicyclo[2.2.2]辛-3-基4-芳基碳酸酯，与(1S)-1-苯基-1,2,3,4-四氢异喹啉反应，形成转化为其药用可接受盐的索利那新碱。该发明还提供了新化合物(3R)-1-azabicyclo[2.2.2]辛-3-基4-芳基碳酸酯，用作制备索利那新碱的中间体及其制备方法。

  公开号：

  WO2010103529A1

文献信息

• METHOD FOR THE PREPARATION OF SOLIFENACIN AND INTERMEDIATE THEREOF
  申请人：Mathad Vijayvitthal Thippannachar

  公开号：US20110319621A1

  公开（公告）日：2011-12-29

  A method for the preparation of solifenacin by reacting quinuclidin-3-ol and bis(aryl) carbonate to form (3R)-1-azabicyclo[2.2.2]oct-3-yl 4-aryl carbonate of formula (IVa); and treating (3R)-1-azabicyclo[2.2.2]oct-3-yl 4-aryl carbonate of formula (IVa) with (1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline of formula (V) in an inert atmosphere to form a Solifenacin base, which is converted into its pharmaceutically acceptable salts. The invention also provides a compound, (3R)-1-azabicyclo[2.2.2]oct-3-yl 4-aryl carbonate of formula (IVa), which is used as an intermediate for the preparation of Solifenacin base and a process for the preparation thereof.

  一种制备索利那新的方法，通过反应三氢喹啉醇和双(芳基)碳酸酯生成公式(IVa)的(3R)-1-氮杂双环[2.2.2]辛-3-基4-芳基碳酸酯; 并在惰性气氛下处理公式(IVa)的(3R)-1-氮杂双环[2.2.2]辛-3-基4-芳基碳酸酯和公式(V)的(1S)-1-苯基-1,2,3,4-四氢异喹啉，形成索利那新碱，再转化为其药学上可接受的盐。本发明还提供一种化合物，公式为(IVa)的(3R)-1-氮杂双环[2.2.2]辛-3-基4-芳基碳酸酯，用作制备索利那新碱的中间体以及其制备方法。
• Method for the preparation of solifenacin and intermediate thereof
  申请人：Megafine Pharma(P) Ltd.

  公开号：US08283470B2

  公开（公告）日：2012-10-09

  A method for the preparation of solifenacin by reacting quinuclidin-3-ol and bis (aryl) carbonate to form (3R)-1-azabicyclo[2.2.2]oct-3-yl 4-aryl carbonate of formula (IVa); and treating (3R)-1-azabicyclo[2.2.2]oct-3-yl 4-aryl carbonate of formula (IVa) with (1S)-1-phenyl- 1,2,3,4-tetrahydroisoquinoline of formula (V) in an inert atmosphere to form a Solifenacin base, which is converted into its pharmaceutically acceptable salts. The invention also provides a compound, (3R)-1-azabicyclo[2.2.2]oct-3-yl 4-aryl carbonate of formula (IVa), which is used as an intermediate for the preparation of Solifenacin base and a process for the preparation thereof.

  一种制备索利吗啉的方法，通过将喹诺啉-3-醇和双(芳基)碳酸酯反应生成式(IVa)的(3R)-1-氮杂双环[2.2.2]辛-3-基4-芳基碳酸酯; 并在惰性气氛下处理式(IVa)的(3R)-1-氮杂双环[2.2.2]辛-3-基4-芳基碳酸酯和式(V)的(1S)-1-苯基-1,2,3,4-四氢异喹啉，形成索利吗啉碱，然后转化成其药学上可接受的盐。该发明还提供一种化合物，式(IVa)的(3R)-1-氮杂双环[2.2.2]辛-3-基4-芳基碳酸酯，用作制备索利吗啉碱的中间体和其制备过程。
• Efficient and single pot process for the preparation of enantiomerically pure solifenacin succinate, an antimuscarinic agent
  作者：Navnath C. Niphade、Kunal M. Jagtap、Anil C. Mali、Pavankumar V. Solanki、Madhukar N. Jachak、Vijayavitthal T. Mathad

  DOI：10.1007/s00706-011-0610-7

  日期：2011.11

  The development of an efficient and economic one-pot process, in which the configuration of the chiral centers of the starting materials is retained, for the preparation of highly pure solifenacin succinate, an antimuscarinic agent, is presented in this communication. The earlier reported processes suffer from the drawbacks of racemization and low yields due to the use of strong base, higher temperatures, and longer reaction times. The present work circumvents these issues by activating (3R)-quinuclidin-3-ol into a mixed active carbonate derivative by treating it with bis(4-nitrophenyl)carbonate. The subsequent reaction of the active carbonate with an enantiomerically pure amine without using any base at ambient temperature provided enantiomerically pure solifenacin with an overall yield of 90%.
• A NEW METHOD FOR THE PREPARATION OF SOLIFENACIN AND NEW INTERMEDIATE THEREOF
  申请人：Megafine Pharma (P) Ltd.

  公开号：EP2406257B1

  公开（公告）日：2019-08-07
• US8283470B2
  申请人：——

  公开号：US8283470B2

  公开（公告）日：2012-10-09