Sodium hydride → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-(2-bromo-5-nitrobenzyl)-4-methyl-1,3-oxazolidin-2-one

Participants

Reaction Steps

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (5.3 g, 16.95 mmol) in THF (100 mL) at 0° C., NaH (746 mg, 60 w/w % in mineral oil, 18.65 mmol, 1.1 eq.) was added in one portion. The resulting foaming mixture was stirred in an ice bath. Additional THF (100 mL) was added into the reaction. The mixture was stirred at 0° C. for 30 min. A solution of 1-bromo-2-(bromomethyl)-4-nitrobenzene (5.0 g, 16.95 mmol) in THF (25 mL) was added. The resulting mixture was stirred cold for 30 min and then allowed to warm to ambient. The reaction was completed in 1.5 h. The reaction was quenched with sat. aqueous NH4Cl (100 mL). Crude mixture was extracted with EtOAc, and dried over Na2SO4. The resulting clear gel was purified by SiO2 (Biotage 40M cartridge, EtOAc/hexane, gradient, 25% to 45%). The titled compound was obtained as a crystalline solid. LC-MS: 529.11 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 8.24 (d, J=2.5 Hz, 1H), 8.07 (dd, J=8.7, 2.8 Hz, 1H), 7.91 (s, 1H), 7.79-7.83 (m, 3H), 5.82 (d, J=7.8 Hz, 1H), 4.82 (d, J=16.2 Hz, 1H), 4.44 (d, J=16.3, 1H), 4.11-4.20 (m, 1H), 0.84 (d, J=6.6 Hz, 3H).

Provenance & Evidence