Acetaldehyde → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(ethylamino)-5-(trifluoromethoxy)benzyl]-4-methyl-1,3-oxazolidin-2-one

Participants

Reaction Steps

To a solution of (4S,5R)-3-[2-amino-5-(trifluoromethoxy)benzyl]-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (80 mg, 0.159 mmol) in dichloroethane (1.6 mL) was added acetaldehyde (9 μL, 0.159 mmol) and NaBH(OAc)3 (67 mg, 0.318 mmol). The reaction was stirred at room temperature, and after 30 minutes acetaldehyde (4.5 μL, 0.80 mmol) was added. After an hour, additional acetaldehyde (4.5 μL, 0.80 mmol) was added. After an additional hour, the reaction was diluted with EtOAc (20 ml) and washed with saturated NH4Cl solution and brine (10 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel (10 to 20% EtOAc/hexanes) afforded (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(ethylamino)-5-(trifluoromethoxy)benzyl]-4-methyl-1,3-oxazolidin-2-one. Rf=0.66 (25% EtOAc/hexanes). LCMS=531.2 (M+1)+. 1H NMR (CDCl3, 500 MHz), 7.88 (s, 1H), 7.73 (s, 2H), 7.10 (dd, J=2.1, 8.8 Hz, 1H), 6.90 (d, J=2.4 Hz, 1H), 6.59 (d, J=8.9 Hz, 1H), 5.66 (d, J=8.4 Hz, 1H), 4.81 (s, 1H), 4.70 (d, J=15.4 Hz, 1H), 4.08 (d, J=15.4 Hz, 1H), 4.06-4.00 (m, 1H), 3.20-3.13 (m, 2H), 1.32 (t, J=7.1 Hz, 3H), 0.78 (d, J=6.6 Hz, 3H).

Provenance & Evidence