(2-amino-1-(3-trifluoromethyl-phenyl)ethanone) p-toluenesulfonate | 1082951-11-8

• 分子结构分类: 有机化合物
• 英文名称: (2-amino-1-(3-trifluoromethyl-phenyl)ethanone) p-toluenesulfonate
• 英文别名: 2-amino-1-(3-trifluoromethyl-phenyl)-ethanone p-toluenesulfonate
• CAS: 1082951-11-8
• 化学式: C₇H₈O₃S*C₉H₈F₃NO
• 分子量: 375.369
• InChiKey: UVEHGGBEAVAEJI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.09
• 重原子数：
  25.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  97.46
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (2-amino-1-(3-trifluoromethyl-phenyl)ethanone) p-toluenesulfonate 在 ammonium acetate 、 1-丙基磷酸酐 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 反应 5.42h， 生成 (4-[4-(3-trifluoromethyl-phenyl)-1H-imidazol-2-yl]-piperidine) dihydrochloride
  参考文献：
  名称：

  Rapid Development and Scale-Up of a 1H-4-Substituted Imidazole Intermediate Enabled by Chemistry in Continuous Plug Flow Reactors

  摘要：

  The development of reactions in a continuous fashion in plug flow tube reactors (PFR) offers unique advantages to the drug development and scale-up process and can also enable chemistry that would be difficult to perform via batch processing. Herein, we report the development of two different continuous flow approaches to a key 1H-4-substituted imidazole intermediate (5). In a first generation approach, rapid optimization and scale-up of a challenging cyclization reaction was demonstrated in a PFR under GMP conditions to afford 29 kg of protected product 2. This material was further processed in batch equipment to deliver di-HCl salt 4. This first generation approach highlights the rapid development of chemistry in research-scale PFRs and speed to material delivery through linear scale up to a pilot-scale PFR under GMP conditions. In a second generation effort, a more efficient synthetic route was developed, and PFRs with automated sampling, dilution, and analytical analysis allowed for rapid and data-rich reaction optimization of both a key cyclization reaction and thermal removal of a Boc protecting group. This work culminated in 1 kg demonstration runs in a 0.22 L PFR for both continuous steps and shows the potential of commercialization from a lab hood footprint (1-2 MT/year).

  DOI：

  10.1021/op200351g
• 作为产物：
  描述：

  间三氟甲基苯乙酮 在 sodium azide 、 溴 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 10.0h， 生成 (2-amino-1-(3-trifluoromethyl-phenyl)ethanone) p-toluenesulfonate
  参考文献：
  名称：

  Rapid Development and Scale-Up of a 1H-4-Substituted Imidazole Intermediate Enabled by Chemistry in Continuous Plug Flow Reactors

  摘要：

  The development of reactions in a continuous fashion in plug flow tube reactors (PFR) offers unique advantages to the drug development and scale-up process and can also enable chemistry that would be difficult to perform via batch processing. Herein, we report the development of two different continuous flow approaches to a key 1H-4-substituted imidazole intermediate (5). In a first generation approach, rapid optimization and scale-up of a challenging cyclization reaction was demonstrated in a PFR under GMP conditions to afford 29 kg of protected product 2. This material was further processed in batch equipment to deliver di-HCl salt 4. This first generation approach highlights the rapid development of chemistry in research-scale PFRs and speed to material delivery through linear scale up to a pilot-scale PFR under GMP conditions. In a second generation effort, a more efficient synthetic route was developed, and PFRs with automated sampling, dilution, and analytical analysis allowed for rapid and data-rich reaction optimization of both a key cyclization reaction and thermal removal of a Boc protecting group. This work culminated in 1 kg demonstration runs in a 0.22 L PFR for both continuous steps and shows the potential of commercialization from a lab hood footprint (1-2 MT/year).

  DOI：

  10.1021/op200351g

文献信息

• WO2008/140947
  申请人：——

  公开号：——

  公开（公告）日：——