反应详情

(2S,4S)-1-[2-[(4-Ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carboxamide (3.70 g) was dissolved in N,N-dimethylformamide (18.5 mL), and while stirring under ice-cooling, trifluoroacetic acid (0.78 mL) was added thereto at an inner temperature of 10° C. or lower. After stirring at an inner temperature of from 0 to 10° C. for 10 minutes, trifluoroacetic anhydride (1.46 mL) was added dropwise thereto, followed by stirring at the same temperature for 1 hour. The reaction solution was poured into ice-water (92.5 mL), potassium carbonate (2.80 g) was added thereto in small portions at an inner temperature of 10° C. or lower and then, after gradually increasing the temperature, potassium carbonate (1.50 g) was further added thereto at an inner temperature of from 35 to 40° C. This was stirred at the same temperature for 10 minutes and then ice-cooled and stirred for 1 hour. The precipitate were collected by filtration, washed with water (37.0 mL) and then dried at 60° C. under reduced pressure, thereby obtaining a white powder of (2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (obtained amount: 2.84 g, yield: 81%).

1. temperaturecooling
2. customat an inner temperature of 10° C.
3. stirringAfter stirring at an inner temperature of from 0 to 10° C. for 10 minutes
4. stirringby stirring at the same temperature for 1 hour
5. additionwas added
6. additionwas further added
7. customof from 35 to 40° C
8. stirringThis was stirred at the same temperature for 10 minutes
9. temperatureice-cooled
10. stirringstirred for 1 hour
11. filtrationThe precipitate were collected by filtration
12. washwashed with water (37.0 mL)
13. customdried at 60° C. under reduced pressure