2-Hydroxy-1,2,3-propanetricarboxylic acid hydrate (1:1) → Tofacitinib Citrate

Participants

Reaction Conditions

Reaction Steps

Water (1 mL) was added to a sample of the product obtained in Example 24 (1.06 g, 2.62 mmol; containing 12.8 wt % of acetone and 0.69% water). Complete dissolution was observed. A solution of citric acid monohydrate (0.67 g, 3.21 mmol) and ammonium acetate (0.25 g, 3.22 mmol) in water (10 mL) was added. A suspension was formed in approximately 5 minutes. The resulting white suspension 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 16 hours to yield tofacitinib citrate (1.25 g; 94%).

Provenance & Evidence