反应详情

A slurry of amorphous ibandronic acid (5 g) in IPA (50 ml) was heated to reflux temperature. Sodium hydroxide (0.63 g, solid) was added, and the reaction mixture was heated at reflux temperature for an additional 4 hours to obtain a pH of 4.19. Then the reaction mixture was cooled to room temperature. Further cooling was performed using an ice-bath. The precipitate was filtered, washed with IPA (2×25 ml), and dried in a vacuum oven at 50° C. for 24 hours to give 5.5 g of ibandronate sodium crystal form K. Form K can exhibit a weight loss of about 10% to about 14% in TGA.

1. temperatureto reflux temperature
2. temperaturethe reaction mixture was heated
3. temperatureat reflux temperature for an additional 4 hours
4. customto obtain a pH of 4.19
5. temperatureFurther cooling
6. filtrationThe precipitate was filtered
7. washwashed with IPA (2×25 ml)
8. customdried in a vacuum oven at 50° C. for 24 hours