反应详情

温度

0 °C

To a solution of (R)—N-benzyl-2-(3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl)acetamide (16.62 g, 40 mmol) in tetrahydrofuran (133 ml) was added sodium borohydride (3.78 g, 100 mmol). The suspension was then cooled to 0° C. and a solution of boron trifluoride tetrahydrofuran (14.56 ml, 132 mmol) in tetrahydrofuran (85 ml). The mixture was warmed up to room temperature (20-25° C.) and stirred for 24 hours. After cooling to 0° C., 1N hydrochloric acid (64 ml, 64 mmol), pH to 1 with 6N hydrochloric acid (17.7 ml, 108 mmol), and the mixture was refluxed for 30 min. Tetrahydrofuran was removed under reduced pressure. The precipitate was collected, washed with water (50 mL). The wet solid was suspended in a mixture of methanol (250 ml) and water (38 ml). The suspension was heated to reflux until complete dissolution; 1N sodium hydroxide (45 ml, 48 mmol) was added (pH 8-9). The crystallization occurred at approx 50° C. The suspension was cooled to 15° C., aged for 3 hours. The precipitate was collected, washed with methanol (33 mL), dried in vacuum at 50° C. to give (R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione (12.5 g, 30.01 mmol, 76% yield).

1. temperatureThe mixture was warmed up to room temperature (20-25° C.)
2. temperatureAfter cooling to 0° C.
3. customTetrahydrofuran was removed under reduced pressure
4. customThe precipitate was collected
5. washwashed with water (50 mL)
6. additionThe wet solid was suspended in a mixture of methanol (250 ml) and water (38 ml)
7. temperatureThe suspension was heated
8. temperatureto reflux until complete dissolution
9. customThe crystallization
10. customoccurred at approx 50° C
11. temperatureThe suspension was cooled to 15° C.
12. waitaged for 3 hours
13. customThe precipitate was collected
14. washwashed with methanol (33 mL)
15. customdried in vacuum at 50° C.