反应详情

温度

24 °C

Amorphous tofacitinib free base (0.70 g, 2.24 mmol) was dissolved in acetone (3 mL). To the clear solution was charged a solution of hydrogen bromide (7.2 mL) in acetone (0.314 M, prepared by addition of 1.93 g of acetyl bromide and 0.50 g of methanol to 50 mL of acetone, 2.26 mmol) in one portion and the white suspension was stirred at 23 to 25° C. for 16 hours. The white suspension was filtered, washed with acetone (2×10 mL) and dried under vacuum (35 torr) for 16 hours to yield 0.55 g of tofacitinib hydrobromide as a white solid. 1H NMR analysis showed a molar ratio of tofacitinib hydrobromide to acetone of approximately 1:0.7 (9.4 wt %) Water content (KF) was 0.88%. A PXRD taken of this sample is shown in FIG. 18.

1. filtrationThe white suspension was filtered
2. washwashed with acetone (2×10 mL)
3. customdried under vacuum (35 torr) for 16 hours