反应详情

温度

24 °C

A solution of 4M hydrogen chloride in 1,4-dioxane (2.353 mmol) was added to a suspension of tofacitinib free base (0.7 g, 2.24 mmol) in dimethyl sulfoxide (3 mL). The clear solution was stirred at 23 to 25° C. (16 hours) without any solid formation. Ethyl acetate (17 mL) was added and the resulting white suspension was heated to 45° C. (2 hours) and cooled to 23 to 25° C. over 4 hours. The white suspension was filtered, washed with ethyl acetate (2×5 mL) and air-dried for 16 hours to yield 830 mg of tofacitinib hydrochloride as a white solid. 1H NMR analysis showed a molar ratio of tofacitinib hydrochloride to dimethyl sulfoxide of approximately 1:1 (18.3 wt %). A PXRD taken of this sample is shown in FIG. 5.

1. temperaturethe resulting white suspension was heated to 45° C. (2 hours)
2. temperaturecooled to 23 to 25° C. over 4 hours
3. filtrationThe white suspension was filtered
4. washwashed with ethyl acetate (2×5 mL)
5. customair-dried for 16 hours