反应详情

A solution of 3-(4-bromo-2-fluoro-benzyl)-7-methoxy benzo[e] [1,3] oxazine-2,4-dione (1.67 g, 4.4 mmol) in ethanol (80 mL, 0.06 M) was cooled to 0° C. and treated with aq KOH (0.673 g, 11.9 mmol, 1.2 M). After 3 h, the reaction was acidified to pH 1–2 with 2 N HCl and extracted with ethyl acetate (3×). The combined organic extracts were washed with saturated aq NaCl, dried over Na2SO4, filtered and concentrated. The crude solid was recrystallized from heptane and ethyl acetate to give N-(4-bromo-2-fluoro-benzyl)-2-hydroxy-4-methoxy-benzamide as a white crystalline solid (1.10 g, 71%): mp 128–129.5° C.; Rf 0.28 (25% ethyl acetate in heptane); 1H NMR (DMSO-d6, 300 MHz) δ 12.70 (br s, 1 H), 9.14 (br t, J=5.2 Hz, 1 H), 7.80 (d, J=8.5 Hz, 1 H), 7.50 (d, J=8.5 Hz, 1 H), 7.40–7.25 (m, 2 H), 6.50–6.48 (m, 2 H), 4.45 (d, J=5.2 Hz, 2 H), 3.75 (s, 3 H). ESI-LC/MS m/z calcd for C15H13BrFNO2: 353.0; found 352.0 (M−1)−. Anal. calcd for C15H13BrFNO2: C, 50.87; H, 3.70; N, 3.95. Found C, 50.70; H, 3.73; N, 3.91.

1. extractionextracted with ethyl acetate (3×)
2. washThe combined organic extracts were washed with saturated aq NaCl
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe crude solid was recrystallized from heptane and ethyl acetate