反応 #601428

反応方程式

water

trimethylaluminium

dichloromethane

ethyl 6-chloro-1-ethyl-2-({2,2,2-trifluoro-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-indole-5-carboxylate

dichloromethane

2,2-Difluoroethanamine

dichloromethane

→

6-chloro-N5-(2,2-difluoroethyl)-1-ethyl-N2-{2,2,2-trifluoro-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide

収率 81.0%

反応条件

後処理

1. 1
   温度The reaction mixture was heated
2. 2
   温度under reflux for 16 h
3. 3
   温度after cooling
4. 4
   抽出The aqueous phase was extracted three times with ethyl acetate
5. 5
   乾燥The combined organic phases were dried over sodium sulphate
6. 6
   その他the solvent was removed under reduced pressure
7. 7
   その他The residue was chromatographed with cyclohexane/ethyl acetate (4/1)

実験手順

2,2-Difluoroethanamine (0.12 g, 1.42 mmol) was dissolved under argon in dichloromethane (2 ml). At room temperature, a solution of trimethylaluminium in dichloromethane (0.71 ml, 1.42 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 30 min and then a solution of ethyl 6-chloro-1-ethyl-2-({2,2,2-trifluoro-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-indole-5-carboxylate (0.078 g, 0.14 mmol) in dichloromethane (2 ml) was added dropwise. The reaction mixture was heated under reflux for 16 h and, after cooling, water was added. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulphate and the solvent was removed under reduced pressure. The residue was chromatographed with cyclohexane/ethyl acetate (4/1) and gave 0.065 g (81% of theory) of 6-chloro-N5-(2,2-difluoroethyl)-1-ethyl-N2-{2,2,2-trifluoro-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide.

出典