反应详情

A solution of sodium hydroxide (0.63 g) in water:IPA (20:80 v/v, 9.5 ml) was added dropwise to a solution of amorphous ibandronic acid (5 g) in water:IPA (20:80 v/v, 53 ml) at reflux temperature. The reaction mixture was heated at reflux temperature for an additional 4 hours to obtain a pH of 3.93-4.01. Then the reaction mixture was cooled to room temperature and stirred for 72 hours. 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 4.4 g of ibandronate sodium crystal form F.

1. temperatureat reflux temperature
2. temperatureThe reaction mixture was heated
3. temperatureat reflux temperature for an additional 4 hours
4. customto obtain a pH of 3.93-4.01
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