Reaction Steps
The title compound was prepared as follows: (R)-(-)-N-carbobenzyloxy-3-methyl-3-[2-fluoro-4-[5-aminomethyl-2-oxo-3-oxazolidinyl]phenyl]azetidine was diluted with 220 mL dichloromethane, cooled to 0° C., and successively treated with 3.7 mL pyridine (46 mmol) and 1.8 mL acetic anhydride (19 mmol) with no observable change. The cooling bath was removed and the reaction mixture was warmed to room temperature for 16 hours. The visually unchanged solution was concentrated to a yellow foam, rediluted with 50 mL dichloromethane, and filtered to remove the remaining insoluble precipitate. The filtrate was purified by LC on 340 g (230-400) silica gel eluting with 2.5% methanol/ethyl acetate to afford 5.85 g (84%) of (S)-N-[[3-[3-fluoro-4-[1-(carbobenzyloxy)-(3-methyl)-3-azetidinyl]-phenyl]-2-oxo-5-oxazolidinyl]methyl]-acetamide as a colorless glass. Rf 0.24 (2.5% methanol/ethyl acetate); [α]D -19° (c 0.9971, methanol); IR (mull) 1754, 1706, 1676, 1516, 1430, 1415, 1357, 1227, 1194, 1075 cm-1 ; 1H NMR (300 MHz, CDCl3) δ 7.42 (dd, 1H, J=2.1 Hz, J=12.9 Hz, aromatic), 7.33 (m, 5H, aromatic), 7.13 (dd, 1H, J=2.2 Hz, J=8.5 Hz, aromatic), 7.04 (t, 1H, J=8.5 Hz, aromatic), 6.56 (bt, 1H, J=6.2 Hz, NH), 5.10 (s, 2H, Ph--CH2), 4.79 (m, 1H, methine), 4.30 (d, 2H, J=8.2 Hz, Ph--C--CH2a s), 4.01 (m, 3H, Ph--C--CH2b s, Ph--N--CH2a), 3.78 (dd, 1H, J=6.7 Hz, J=9.1 Hz, Ph--N--CH2b), 3.64 (m, 2H, NH--CH2 s ), 2.02 (s, 3H, O=C--CH3), 1.60, (s, 3H, Ph--C--CH3); 13C NMR (75 MHz, CDCl3) 171.2, 160.3 (d, JCF =246 Hz), 156.6, 154.2, 137.9 (d, JCF =11 Hz), 136.5, 128.9 (d, JCF =14 Hz), 128.4, 127.9, 127.2 (d, JCF =7 Hz), 113.2 (d, JCF =2 Hz), 106.4 (d, JCF =28 Hz), 72.0, 66.6, 60.7, 60.3, 47.3, 41.7, 36.1, 28.1, 22.9; Anal. Calcd for C24H26N3O5F1 : C, 63.29; H, 5.75; N, 9.23. Found: C, 62.98; H, 5.96; N, 8.98.
