反应详情

温度

5 °C

Mixture of 100 g (0.186 mol) (3S)-tetrahydro-3-furyl N-[(1S,2R)-1-benzyl-2-hydroxy-3-(N-isobutyl-4-nitrobenzene sulphonamido)propyl]carbamate (IV) and 200 ml pyridine was cooled to 0-10° C. and 70.0 g (0.456 mol) of POCl3 was added and stirred at ambient temperature for 4 hours, 400 ml methyl isobutyl ketone was added, cooled and 1:1 conc. HCl-water was added. Mixture was heated to 50° C. for 1 hour, cooled to 25-30° C. Organic layer was separated, washed with water and partially concentrated; 500 ml water and 31.5 g sodium bicarbonate was added and stirred. The organic layer was separated and 100 ml ethylacetate, 400 ml methanol and 5.0 g Pd/C was added. The reaction mass was stirred under hydrogen pressure for 4 hours at 30° C. The mixture was filtered, catalyst washed with methanol. The filtrate was heated to 50° C. and 33.0 g (0.186 mol) calcium acetate monohydrate in 100 ml water was added and stirred for 30 minutes. Cooled to 30° C. and stirred. Solid was filtered, washed with 1:1 mixture of methanol-water and dried to obtain crude fosamprenavir calcium.

1. temperaturecooled
2. temperatureMixture was heated to 50° C. for 1 hour
3. temperaturecooled to 25-30° C
4. customOrganic layer was separated
5. washwashed with water
6. concentrationpartially concentrated
7. addition500 ml water and 31.5 g sodium bicarbonate was added
8. stirringstirred
9. customThe organic layer was separated
10. addition100 ml ethylacetate, 400 ml methanol and 5.0 g Pd/C was added
11. stirringThe reaction mass was stirred under hydrogen pressure for 4 hours at 30° C
12. filtrationThe mixture was filtered
13. washcatalyst washed with methanol
14. temperatureThe filtrate was heated to 50° C.
15. stirringstirred for 30 minutes
16. temperatureCooled to 30° C.
17. stirringstirred
18. filtrationSolid was filtered
19. washwashed with 1:1 mixture of methanol-water
20. customdried