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

Participants

Reaction Conditions

Reaction Steps

Water (0.5 mL) was added to amorphous tofacitinib hydrochloride (600 mg, 1.719 mmol). Complete dissolution was observed. A solution of citric acid monohydrate (542 mg, 2.579 mmol) and N,N-Diisopropylethylamine (270 mg, 2.063 mmol) in water (10 mL) was added. A white suspension was formed in approximately 1 to 2 minutes. The suspension was stirred at 23 to 25° C. for 12 hours, filtered, washed with water (2×10 mL) and acetone (5 mL). The damp cake was dried under vacuum (5 torr) at 23 to 25° C. for 4 hours to yield tofacitinib citrate (690 mg; 80%).

Provenance & Evidence