Hydrochloric Acid → Tofacitinib Citrate

Participants

Reaction Steps

Water (1 mL) was added to a sample of the product obtained in Example 24 (1.01 g, 2.51 mmol; containing 12.8 wt % of acetone and 0.69% water). Complete dissolution was observed. A solution of citric acid monohydrate (0.64 g, 3.07 mmol) and cesium carbonate (1.02 g, 3.13 mmol) in water (10 mL) was added. A suspension was formed in approximately 1 to 2 minutes. The suspension was then treated with 4M hydrogen chloride in 1,4-dioxane (2.60 mmol). The resulting white suspension (pH=3) was stirred at 23 to 25° C. for 16 hours, filtered and washed with water (2×5 mL). The damp cake was dried under vacuum (34 torr) at 40 to 45° C. for 56 hours to yield tofacitinib citrate (1.09 g; 86%).

Provenance & Evidence