To a solution of (1S,2S,3R,4R,5S)-2-amino-3,4-bis(benzyloxy)-5-(fluoromethyl)cyclohexanol (182 mg, 0.507 mmol) in THF (4 mL) at room temperature was added a solution of ethylthioisocyanate (55 mg, 0.63 mmol) in THF (1 mL). The mixture was stirred at room temperature for 18 h. The solvent was evaporated to give a colorless syrup. This was dissolved in acetone (3 mL) and MeI (144 mg, 1.01 mmol) was added. The mixture was stirred at room temperature for 6 h. The reaction was diluted with saturated aqueous NaHCO3 (20 mL) and extracted with DCM (3×10 mL). The extracts were dried with Na2SO4 and the solvents were evaporated to give (3aS,4R,5R,6S,7aS)-4,5-bis(benzyloxy)-N-ethyl-6-(fluoromethyl)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazol-2-amine as a white solid (209 mg, 100%) which was pure enough for next reaction. MS m/z 413.2 (M+1, 100%); 1H NMR (400 MHz, CDCl3) δ 7.27-7.39 (m, 10H), 4.86 (d, J=11.7 Hz, 1H), 4.80 (d, J=11.2 Hz, 1H), 4.70 (d, J=11.6 Hz, 1H), 4.69-4.73 (m, 1H), 4.64 (dd, J=9.0 Hz, 4.5 Hz, 0.5H), 4.45-4.53 (m, 1H), 4.48 (d, J=11.2 Hz, 1H), 4.35 (dd, J=8.9 Hz, 2.9 Hz, 0.5H), 4.09 (dd, J=8.0 Hz, 5.2 Hz, 1H), 3.67 (t, J=5.6 Hz, 1H), 3.46 (dd, J=9.3 Hz, 6.1 Hz, 1H), 3.16-3.29 (m, 2H), 2.12 (dt, J=14.6 Hz, 2.9 Hz, 1H), 1.91-2.06 (m, 1H), 1.79-1.87 (m, 1H), 1.15 (t, J=7.2 Hz, 3H).
