Ethyl Acetate → HCID 131729737, compound

Participants

Reaction Conditions

Reaction Steps

To a 250 ml round bottom flask, equipped with a magnetic stirrer and a reflux condenser, was added Sitagliptin base (12.0 g) and ethyl acetate (120 ml). The mixture was heated to 60° C. for dissolution. A solution of L-malic acid (3.95 g) in absolute ethanol (24 ml) was added to the above solution dropwise over 15 minutes. During the addition, the heating was stopped and the mixture was cooled slowly. When the addition was completed the temperature in the oil bath was 43° C. The solution was cooled to room temperature (˜20° C.) and stirred overnight. After 3 days about 60 g of solvents were distilled out and the solution was stirred at room temperature over 10 days, during this time precipitation as a soft white block occurred. Ethyl acetate (110 ml) was added in order to facilitate filtration and the mixture was stirred for several minutes. The product was isolated by vacuum filtration, washed with ethyl acetate (40 ml) and dried in a vacuum oven at 50° C. for 24 hours and then for additional 48 hours at room temperature (15-25° C.) to obtain Sitagliptin L-malate crystalline form I3 (13.86 g, 87% yield).

Provenance & Evidence