Reaction Steps
To a slurry of 20% palladium on carbon (10 g, 0.06 equiv) in EtOH (1 L) was added a solution of diastereomeric mixture of 3-{[(2R)-3-(2-fluorophenyl)-1-methyl-5-oxo(3-pyrrolin-2-yl)carbonyl(4S)-4-benzyl-1,3-oxazolidin-2-one and (4S)-3-{[(2S)-3-(2-fluorophenyl)-1-methyl-5-oxo(3-pyrrolin-2-yl)]carbonyl}-4-benzyl-1,3-oxazolidin-2-one (154 g, 0.36 mol) in EtOH (1 L) and the resulting mixture was vigorously stirred under a H2 atmosphere (1 Atm) for 17 h. The reaction mixture was filtered through a pad of Celite®. NMR analysis of the filtrate showed only partial reduction, and the reaction mixture was treated with 10% palladium on carbon (Degussa type, 30 g, 0.1 equiv) in EtOH (4 L). After stirring under a H2 atmosphere (1 Atm) for 17 h, the reaction mixture was filtered through a pad of Celite®. The filtrate was concentrated under reduced pressure onto silica gel (250 g), then filtered through a plug of silica gel eluting with EtOAc. The filtrate was concentrated under reduced pressure onto silica gel (400 g) and purified by flash chromatography (2.5 kg silica gel, gradient from 25% to 60% EtOAc/hex) to afford (4S)-3-{[(2S,3S)-3-(2-fluorophenyl)-1-methyl-5-oxopyrrolidin-2-yl]carbonyl}-4-benzyl-1,3-oxazolidin-2-one (48 g, 30%) as a yellow solid: TLC (50% EtOAc/hex) Rf 0.22; 1H NMR (CDCl3; rotomeric mixture) δ 2.63 (dd, J=4.9, 9.5 Hz, 1H), 2.74-2.85 (m, 4H), 3.07 (dd, J=3.4, 13.2 Hz, 1H), 3.34 (t, J=8.3 Hz, 1H), 3.84-4.09 (m, 3H), 4.27 (dd, J=9.6, 18.8 Hz, 1H), 5.77 (d, J=8.8 Hz, 1H), 6.95-7.26 (m, 10H); HPLC ESMS m/z (rel abundance) 397 (MH+, 75%); and 3-{[(2R,3R)-3-(2-fluorophenyl)-1-methyl-5-oxopyrrolidin-2-yl]carbonyl}(4S)-4-benzyl-1,3-oxazolidin-2-one (48 g, 30%) as a yellow solid: TLC (50% EtOAc/hex) Rf 0.13; 1H NMR (CDCl3; rotomeric mixture) δ 1.63 (dd, J=11.2, 13.4 Hz, 1H), 2.64 (dd, J=2.8, 13.1 Hz, 1H), 2.75-2.93 (m, 5H), 3.95 (dd, J=3.4, 9.2 Hz, 1H), 4.09 (t, J=7.8 Hz, 1H), 4.40-4.50 (m, 2H), 5.77 (d, J=8.6 Hz, 1H), 7.04-7.12 (m, 4H), 7.21-7.32 (m, 5H); HPLC ES-MS m/z (rel abundance) 397 (MH+, 90%); and a mixture of the two diastereomers (17 g, 11%).
