反应详情

Zinc powder (10.1 g) was added to a suspension of (3aR,4S,6aS)-6a-(2,3-Difluorophenyl)-4-((trityloxy)methyl)tetrahydrofuro[3,4-c]isoxazole, obtained in Preparation Example 4-(22), (7.76 g) in acetic acid (75 ml) at RT. The mixture was stirred for 11.5 h at RT then the solid was removed by filtration through celite. The filtrate was concentrated in vacuo, then the residue was dissolved with EtOAc. 28% ammonia aqueous solution was added slowly, and the organic layer was separated, washed with brine, and dried over MgSO4. The solid was removed by filtration and the filtrate was concentrated under reduced pressure. Zinc powder (10.1 g) was added to the suspension of the residue in acetic acid (75 ml) at RT. After the mixture was stirred for 11.5 h at same temperature, the solid was removed by filtration through celite. The filtrate was concentrated in vacuo, then the residue was dissolved with EtOAc. 28% ammonia aqueous solution was added slowly, and the organic layer was separated, washed with brine, and dried over MgSO4. The solid was removed by filtration, and the filtrate was concentrated under reduced pressure. The crude mixture was purified by amino silica gel column chromatography (gradient from 50% to 100% EtOAc in heptane) to afford the titled compound (7.04 g) as a white solid. 1H-NMR (400 MHz, CDCl3) δ (ppm): 2.60-2.64 (m, 1H), 3.27 (d, J=4.8 Hz, 2H), 3.61-3.65 (m, 1H), 3.89-3.94 (m, 2H), 4.30 (d, J=9.2 Hz, 1H), 4.33-4.37 (m, 1H), 7.04-7.16 (m, 2H), 7.20-7.30 (m, 10H), 7.40-7.43 (m, 6H)

1. customat RT
2. customthe solid was removed by filtration through celite
3. concentrationThe filtrate was concentrated in vacuo
4. dissolutionthe residue was dissolved with EtOAc
5. addition28% ammonia aqueous solution was added slowly
6. customthe organic layer was separated
7. washwashed with brine
8. dry with materialdried over MgSO4
9. customThe solid was removed by filtration
10. concentrationthe filtrate was concentrated under reduced pressure
11. additionZinc powder (10.1 g) was added to the suspension of the residue in acetic acid (75 ml) at RT
12. stirringAfter the mixture was stirred for 11.5 h at same temperature
13. customthe solid was removed by filtration through celite
14. concentrationThe filtrate was concentrated in vacuo
15. dissolutionthe residue was dissolved with EtOAc
16. addition28% ammonia aqueous solution was added slowly
17. customthe organic layer was separated
18. washwashed with brine
19. dry with materialdried over MgSO4
20. customThe solid was removed by filtration
21. concentrationthe filtrate was concentrated under reduced pressure
22. customThe crude mixture was purified by amino silica gel column chromatography (gradient from 50% to 100% EtOAc in heptane)