反应详情

温度

35 °C

4-Fluoro-6-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one free base (1.499 mmol, 500 mg, 1 wt) was weighed into a 250 ml round bottomed flask, citric acid (1 eq, 1.499 mmol, 288 mg,) was added. Acetonitrile (95 vol. 47.5 ml) was added and a white slurry obtained, dissolution was not achieved with heating using a hot air gun. The slurry was magnetically stirred at 35° C. for four days under nitrogen. The solid was cooled and isolated by vacuum filtration and washed with acetonitrile (10 vol. 5 ml). The solid (1.0 g not dried) was recombined with the mother liquors plus acetonitrile (29 vol., 14.5 ml) and n-propanol (22 vol. 11 ml) was added. The slurry was stirred at ambient temperature overnight. The solid was isolated by vacuum filtration and washed with acetonitrile (10 vol, 5 ml). The white solid was dried under vacuum at 60° C. for 25 hours. 506 mg, 64%.

1. customa white slurry obtained
2. dissolutiondissolution
3. temperaturewith heating
4. temperatureThe solid was cooled
5. customisolated by vacuum filtration
6. washwashed with acetonitrile (10 vol. 5 ml)
7. customThe solid (1.0 g not dried)
8. additionwas added
9. stirringThe slurry was stirred at ambient temperature overnight
10. customThe solid was isolated by vacuum filtration
11. washwashed with acetonitrile (10 vol, 5 ml)
12. customThe white solid was dried under vacuum at 60° C. for 25 hours