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 (1.01 g, 2.51 mmol; containing 12.8 wt % of acetone and 0.69% water). Complete dissolution was observed. A solution of citric acid monohydrate (0.65 g, 3.10 mmol) and potassium acetate (0.28 g, 2.84 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 (1.18 g; 93%).

Provenance & Evidence