反应详情

温度

45 °C

A solution of approximately 17 wt % hydrogen chloride in isopropanol (7.684 mmol) was added to a suspension of tofacitinib free base (2.0 g, 6.402 mmol) in acetone (28 mL). The suspension was heated to 45° C. for 4 hours and then cooled to 23 to 25° C. Small amounts of solids were adhered to the walls of the flask which were broken with a spatula. The white suspension was stirred at 23 to 25° C. for 22 hours, filtered, washed with acetone (2×10 mL) and dried under vacuum (5 torr) at 40° C. (3 hours) to yield tofacitinib hydrochloride (2.36 g) as a white solid. 1H NMR analysis showed a molar ratio of tofacitinib hydrochloride to acetone of approximately 1:0.82 (12.0 wt %). Water content (KF) was 1.89%. A PXRD taken of the sample is shown in FIG. 3.

1. temperaturecooled to 23 to 25° C
2. filtrationfiltered
3. washwashed with acetone (2×10 mL)
4. customdried under vacuum (5 torr) at 40° C. (3 hours)