反应详情

To a solution of (3aS,4R,5R,6R,7aS)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-hexahydrobenzo[d]oxazol-2(3H)-one (237 mg, 0.500 mmol) in dry DCM (3.5 mL) was added 4 molecule sieves (200 mg) followed by trimethyloxonium tetrafluoroborate (370 mg, 2.50 mmol). The mixture was stirred under nitrogen at room temperature for 24 h. Pyrrolidine (355 mg, 5.00 mmol) was added followed by THF (2 mL). The mixture was stirred at room temperature for another 24 h. The mixture was diluted with satd. aqueous NaHCO3 (20 mL), extracted with EtOAc (2×15 mL). The combined extracts were washed with brine and dried over Na2SO4. Solvents were evaporated under reduced pressure. The crude product was purified by silica gel column chromatography, eluted with 5% MeOH in DCM and then with 94:5:1 DCM-MeOH—NH4OH (28% aqueous) to give (3aS,4R,5R,6R,7aS)-4,5-bis(benzyloxy)-6-((benzyloxy)methyl)-2-(pyrrolidin-1-yl)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazole (54.5 mg, 21%) as a syrup. 1H NMR (400 MHz, CDCl3) δ 7.41-7.25 (m, 15H), 4.90 (d, J=11.7 Hz, 1H), 4.79 (d, J=11.2 Hz, 1H), 4.73 (d, J=11.7 Hz, 1H), 4.72 (m, 1H), 4.47 (s, 2H), 4.46 (d, J=11.2 Hz, 1H), 4.06 (dd, J=7.9, 5.4 Hz, 1H), 3.65 (t, J=5.9 Hz, 1H), 3.59 (dd, J=9.0, 5.2 Hz, 1H), 3.53-3.48 (m, 2H), 3.35 (t, J=6.6 Hz, 4H), 2.19 (dt, J=14.8, 3.3 Hz, 1H), 2.08-2.00 (m, 1H), 1.90-1.82 (m, 5H).

1. stirringThe mixture was stirred at room temperature for another 24 h
2. additionThe mixture was diluted with satd
3. extractionaqueous NaHCO3 (20 mL), extracted with EtOAc (2×15 mL)
4. washThe combined extracts were washed with brine
5. dry with materialdried over Na2SO4
6. customSolvents were evaporated under reduced pressure
7. customThe crude product was purified by silica gel column chromatography
8. washeluted with 5% MeOH in DCM