Citric Acid → Tofacitinib Citrate

Participants

Reaction Steps

Form APO-A tofacitinib hydrochloride (0.80 g, 2.29 mmol) was dissolved in water (0.80 mL). A solution of citric acid (0.53 g, 2.75 mmol) and 1,8-diazabicycloundec-7-ene (DBU) (0.38 g, 2.52 mmol) in water (8 mL) was charged under stirring at room temperature. Solids started to form 1-2 minutes following addition. The suspension was stirred at room temperature for 4 hours then filtered and washed with water (2×5 mL) and acetone (1×3 mL). The filtered solids were dried under vacuum (35 torr) at 40° C. for approximately 5 hours to yield 1.03 g of tofacitinib citrate (1.03 g; 89%) as a white solid.

Provenance & Evidence