Isopropanol → Zoledronate disodium tetrahydrate

Participants

Reaction Steps

A solution of sodium hydroxide (1.4 g) in a mixture of water (80% v/v)/IPA (20% v/v, 10 volumes per grams of ZLD-Ac form I) (38 ml) was added drop-wise to a suspension of Zoledronic acid form I (5.0 g) in a mixture of water (80% v/v)/IPA (20% v/v, 10 volumes per grams of ZLD-Ac) (212 ml) at reflux temperature. The reaction mixture was heated at reflux temperature for additional 16 hours. Then the reaction mixture was cooled to room temperature and the solution was evaporated to dryness. The obtained solid was dried in a vacuum oven at 50° C. for 5 hours to give 5.2 g (78%) of Zoledronate disodium crystal form VI (LOD by TGA=15.4%). Purity by HPLC 99.9%.

Provenance & Evidence