Isopropanol → Zoledronate disodium tetrahydrate

Participants

Reaction Conditions

Reaction Steps

A 0.5 liter reactor equipped with a mechanical stirrer, a thermometer and a reflux condenser was loaded with Zoledronic acid form I (10.0 g) and water (260 ml). The suspension was heated to 80° C. to obtain a clear solution. Sodium hydroxide (pearls, 2.84 g) was added. A pH test of the sodium salt showed pH=7.35. The solution was cooled to 60° C. and IPA (10.5 ml) was added. The reaction mixture was cooled to room temperature during 2 hours and was stirred at this temperature for about 16 hours. After cooling to 5° C. and stirring at this temperature for 2 hours, the solution was evaporated to dryness to obtain a white solid. The obtained solid was reslurried in water (50 ml) and cooled to 4° C. The product was then isolated by filtration and dried in a vacuum oven at 50° C. for 24 hours to obtain 3.2 g of Zoledronate disodium crystal form VII (24%) (pH=7.27). Purity by HPLC 100.0%.

Provenance & Evidence