反应详情

温度

30 °C

A 4-neck RBF was charged under nitrogen flow with: 10 g of Midazolam (IV) (prepared according to example 2) and 40 mL of Ethanol. The slurry was stirred until complete dissolution at 25/30° C. In an other flask was prepared the following solution: 3.72 g of maleic acid are dissolved in 15 mL of Ethanol. The slurry was stirred until complete dissolution at 25/30° C. The maleic acid solution is dropped in 30/40 minutes and keeping T=25/30° C. into the solution containing Midazolam. The slurry was cooled down at −15° C. in one hour and kept at that temperature for at least 2 hours. The slurry was then filtered and the cake was washed with 40 mL of cool Ethanol. The filter was discharged and the product was dried at 40° C. under vacuum for 2 hours and then at 60° C. for 8 hours. 12.8 g of Midazolam Maleate as white solid were collected (Molar yield=94.5%). m.p.=149-152° C. (by DSC).

1. customIn an other flask was prepared the following solution
2. stirringThe slurry was stirred until complete dissolution at 25/30° C
3. custom30° C.
4. temperatureThe slurry was cooled down at −15° C. in one hour
5. waitkept at that temperature for at least 2 hours
6. filtrationThe slurry was then filtered
7. washthe cake was washed with 40 mL of cool Ethanol
8. customthe product was dried at 40° C. under vacuum for 2 hours
9. custom12.8 g of Midazolam Maleate as white solid were collected (Molar yield=94.5%)