反应详情

温度

24 °C

A solution of 4M hydrogen chloride in 1,4-dioxane (g, 2.353 mmol) was added to a suspension of tofacitinib free base (0.7 g, 2.24 mmol) in N,N-dimethylformamide (3 mL). The clear solution was stirred at 23 to 25° C. (3 hours) without any solid formation. Ethyl acetate (2 mL) was added and the resulting turbid solution was stirred at room temperature (16 hours) resulting in the formation of a white suspension. An additional portion (5 mL) of ethyl acetate was added and stirring was continued at 23 to 25° C. for 7 hours. The white suspension was filtered, washed with ethyl acetate (2×5 mL) and air-dried for 16 hours to yield tofacitinib hydrochloride (860 mg). 1H NMR analysis showed a molar ratio of tofacitinib hydrochloride to N,N-dimethylformamide of approximately 1:0.8 (14.3 wt %). A PXRD taken of this sample is shown in FIG. 4.

1. stirringthe resulting turbid solution was stirred at room temperature (16 hours)
2. customresulting in the formation of a white suspension
3. stirringstirring
4. waitwas continued at 23 to 25° C. for 7 hours
5. filtrationThe white suspension was filtered
6. washwashed with ethyl acetate (2×5 mL)
7. customair-dried for 16 hours