Citric Acid → Tofacitinib Citrate

Participants

Reaction Conditions

Reaction Steps

A stirred solution of (3R,4R)-3-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile (230 mg/0.74 mmol) dissolved in 23 mL of acetone was heated to 40° C. To this solution was added 155 mg (0.81 mmol) of finely ground citric acid. The resulting mixture stirred at 40° C. for 2 hours, then at 30° C. for 4 hours followed by stirring at room temperature for an additional 18 hours. At this point, the solids were collected by filtration, washed with acetone and dried in vacuo affording 280 mg (75%) of the title compound as a white crystalline solid.

Provenance & Evidence