Reaction Steps
To a solution of (3aS,4R,5R,6S,7aS)-4,5-bis(benzyloxy)-6-(fluoromethyl)hexahydrobenzo[d]oxazol-2(3H)-one (193 mg, 0.503 mmol) in DCM (4 mL) at room temperature was added 4 A molecular sieves (130 mg) followed by trimethyloxonium tetrafluoroborate (372 mg, 2.52 mmol). The mixture was stirred at room temperature under N2 for 24 h. Azetidine hydrochloride (236 mg, 2.52 mmol) and a solution of Et3N (279 mg) in THF (2.0 mL) was added. The mixture was stirred at room temperature for another 48 h. The reaction was diluted with saturated aqueous NaHCO3 (20 mL) and extracted with DCM (2×15 mL). The extracts were dried with Na2SO4 and the solvents were evaporated to give the crude product. This was purified by silica gel column, eluted with 2%-5% 2 M NH3 MeOH solution in DCM to yield (3aS,4R,5R,6S,7aS)-2-(azetidin-1-yl)-4,5-bis(benzyloxy)-6-(fluoromethyl)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazole as a white solid (80.0 mg, 38%). MS m/z 425.2 (M+1, 100%); 1H NMR (500 MHz, CDCl3) δ 7.28-7.36 (m, 10H), 4.93-4.96 (m, 1H), 4.77 (d, J=11.7 Hz, 1H), 4.71 (d, J=11.1 Hz, 1H), 4.65 (d, J=11.7 Hz, 1H), 4.54 (dd, J=9.0 Hz, 5.0 Hz, 1H), 4.49 (d, J=11.2 Hz, 1H), 4.43-4.46 (m, 1H), 4.43 (d, J=11.1 Hz, 1H), 4.34 (dd, J=9.0 Hz, 4.7 Hz, 1H), 4.20 (dd, J=8.3 Hz, 3.7 Hz, 1H), 3.88-3.99 (m, 4H), 3.86 (t, J=4.3 Hz, 1H), 3.53 (t, J=5.7 Hz, 1H), 2.09-2.19 (m, 4H), 1.81-1.87 (m, 1H).
