Methanol → Fosamprenavir Calcium

Calcium salt of (3S)-tetrahydrofuran-3-yl[(2S,3R)-4-{(2-methylpropyl)[(4-nitrophenyl)sulfonyl]amino}-1-phenyl-3-(phosphonooxy)butan-2-yl]carbamate (5 g) was added into a mixture of methanol (50 mL) and ethyl acetate (50 mL) at 20° C. to 25° C. and stirred for 20 minutes. The reaction mixture was filtered through Celite bed and the bed was washed with methanol:ethyl acetate (1:1, 12.5 mL). Palladium-carbon (10%; 1 g) was added to the filtrate and stirred at 20° C. to 25° C. under hydrogen pressure 30 to 40 psi for 4 to 5 hours. The resultant mixture was filtered over Celite bed and the bed was washed with methanol:ethylacetate (1:1; 12.5 mL). The solvent was removed from the filtrate under vacuum at 40° C. to 45° C. to obtain a residue. De-ionized water (50 mL) was added to the residue and stirred at 90° C. to 95° C. for 2 to 3 hours. The reaction mixture was cooled to 20° C. to 25° C. and stirred for 2 hours further. The solid obtained was filtered, washed with de-ionized water (10 mL) and dried at 40° C. Industrial methylated spirit (52.5 mL) was added to the dried solid at 20° C. to 25° C., heated at 70° C. to 72° C., stirred for 15 minutes, filtered at hot condition through Celite bed and washed with hot industrial methylated spirit (17.5 mL). The filtrate was heated at 70° C. to 72° C. followed by the addition of de-ionized water (10.5 mL). The mixture was cooled to 20° C. to 25° C., stirred for 2 hours further, filtered, washed industrial methylated spirit: de-ionized water (1:1, 10 mL) and dried at 40° C. under vacuum to obtain the title compound.

1. filtrationThe reaction mixture was filtered through Celite bed
2. washthe bed was washed with methanol:ethyl acetate (1:1, 12.5 mL)
3. additionPalladium-carbon (10%; 1 g) was added to the filtrate
4. stirringstirred at 20° C. to 25° C. under hydrogen pressure 30 to 40 psi for 4 to 5 hours
5. filtrationThe resultant mixture was filtered over Celite bed
6. washthe bed was washed with methanol:ethylacetate (1:1; 12.5 mL)
7. customThe solvent was removed from the filtrate under vacuum at 40° C. to 45° C.
8. customto obtain a residue
9. stirringstirred at 90° C. to 95° C. for 2 to 3 hours
10. temperatureThe reaction mixture was cooled to 20° C. to 25° C.
11. stirringstirred for 2 hours further
12. customThe solid obtained
13. filtrationwas filtered
14. washwashed with de-ionized water (10 mL)
15. customdried at 40° C
16. additionIndustrial methylated spirit (52.5 mL) was added to the dried solid at 20° C. to 25° C.
17. temperatureheated at 70° C. to 72° C.
18. stirringstirred for 15 minutes
19. filtrationfiltered at hot condition through Celite bed
20. washwashed with hot industrial methylated spirit (17.5 mL)
21. temperatureThe filtrate was heated at 70° C. to 72° C.
22. additionfollowed by the addition of de-ionized water (10.5 mL)
23. temperatureThe mixture was cooled to 20° C. to 25° C.
24. stirringstirred for 2 hours further
25. filtrationfiltered
26. washwashed industrial methylated spirit
27. dry with materialde-ionized water (1:1, 10 mL) and dried at 40° C. under vacuum

ORD record

ord-6bac567ecc6d43f3bf7d2fa3ab51c0ad

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09085592B2