反应详情

温度

50 °C

A stirring solution of N-(4-bromo-2-fluoro-benzyl)-4-fluoro-2-hydroxy-5-methyl-benzamide (1.69 g, 4.76 mmol) in acetone (24 mL, 0.2 M) was treated with an aq K2CO3 solution (3.6 mL, 2 M, 7.12 mmol) and ethylbromoacetate (0.63 mL, 5.69 mmol) in acetone (24 mL, 0.2 M) and heated to 50° C. for 2.5 h. After cooling to room temperature, the solution was concentrated, acidified to pH 1 with 2 N HCl, and diluted with ethyl acetate (100 mL) and washed with 50 mL of saturated aq NaCl. The organic layer was dried over Na2SO4, filtered, and concentrated to provide [2-(4-bromo-2-fluoro-benzylcarbamoyl)-5-fluoro-4-methyl-phenoxy]-acetic acid ethyl ester (1.95, 93%) as a white solid: mp 128–129° C.; Rf 0.42 (30% ethyl acetate in heptane); 1H NMR (CDCl3, 300 MHz) δ 8.79 (bd t, J=4.5 Hz, 1 H), 8.10 (d, J=9.0 Hz, 1 H), 7.34 (t, J=8.3 Hz, 1 H), 7.26–7.23 (m, 1 H), 7.21 (t, J=2.3 Hz, 1 H), 6.53 (d, J=10.5 Hz, 1 H), 4.66 (d, J=3.9 Hz, 1 H), 4.65 (s, 2 H), 4.28 (q, J=7.2 Hz, 2 H), 2.23 (bd d, J=1.5 Hz, 3 H), 1.30 (t, J=7.2 Hz, 3H); Anal. calcd for C19H18BrFNO4: C, 51.60; H, 4.10; N, 3.17. Found C, 51.65; H, 4.19; N, 3.10.

1. temperatureAfter cooling to room temperature
2. concentrationthe solution was concentrated
3. additiondiluted with ethyl acetate (100 mL)
4. washwashed with 50 mL of saturated aq NaCl
5. dry with materialThe organic layer was dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated