1-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(methylamino)ethanone hydrochloride | 1370337-76-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(methylamino)ethanone hydrochloride
• CAS: 1370337-76-0
• 化学式: C₁₀H₉F₄NO*ClH
• 分子量: 271.642
• InChiKey: ITIMWYWQJREGDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.67
• 重原子数：
  17.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  29.1
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  1-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(methylamino)ethanone hydrochloride 在 N-甲基吗啉 、 ammonium acetate 、 溶剂黄146 、 1-丙基磷酸酐 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 乙酸乙酯 为溶剂， 反应 0.67h， 生成 4-[4-(4-fluoro-3-trifluoromethylphenyl)-1-methyl-1H-imidazol-2-yl]piperidine
  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：

  5-溴-2-氟三氟甲苯 在 盐酸 、 异丙基氯化镁 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 5.17h， 生成 1-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(methylamino)ethanone hydrochloride
  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