A stirred solution of (4S,5R)-3-[2-amino-5-(trifluoromethoxy)benzyl]-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (Intermediate 16; 820 mg; 1.63 mmol) and ethyl (trans-4-formylcyclohexyl)acetate (Intermediate 14; 270 mg; 1.36 mmol) in toluene (8 mL) was heated at reflux for 3 h. The reaction was concentrated in vacuo and redissolved in EtOH (8 mL). Sodium borohydride (103 mg; 2.72 mmol) was added and the reaction stirred at room temperature for 14 h. The reaction was quenched with sat. NH4Cl and partitioned between EtOAc (25 mL) and H2O (25 mL). The aqueous layer was re-extracted with EtOAc (3×25 mL) and the combined organic layers were washed with brine (25 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography (0-25% EtOAc/hexanes gradient) to afford ethyl [trans-4-({[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethoxy)phenyl]amino}methyl)cyclohexyl]acetate as a yellow gum. LCMS=685.1 (M+1)+. 1H NMR (CDCl3, 500 MHz): δ 7.89 (s, 1 H), 7.73 (s, 2 H), 7.13 (d, J=8.7 Hz, 1 H), 6.92 (d, J=2.3 Hz, 1 H), 6.72 (d, J=9.0 Hz, 1 H), 5.66 (d, J=8.2 Hz, 1 H), 4.74 (d, J=15.6 Hz, 1 H), 4.14-4.02 (m, 4 H), 3.05-2.97 (m, 2 H), 2.19 (d, J=6.9 Hz, 2 H), 1.96-1.90 (m, 2 H), 1.85-1.78 (m, 2 H), 1.71-1.62 (m, 1 H), 1.51-1.39 (m, 2 H), 1.25 (t, J=7.1 Hz, 3 H), 1.12-1.03 (m, 3 H), 0.80 (d, J=6.4 Hz, 3 H).
