Ethyl bromoacetate → (2-(4-Bromo-2-fluoro-benzylcarbamoyl)-5-fluoro-4-methyl-phenoxy]-acetic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

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, 1H), 8.10 (d, J=9.0 Hz, 1H), 7.34 (t, J=8.3 Hz, 1H), 7.26-7.23 (m, 1H), 7.21 (t, J=2.3 Hz, 1H), 6.53 (d, J=10.5 Hz, 1H), 4.66 (d, J=3.9 Hz, 1H), 4.65 (s, 2H), 4.28 (q, J=7.2 Hz, 2H), 2.23 (bd d, J=1.5 Hz, 3H), 1.30 (t, J=7.2 Hz, 3H); Anal. calcd for C19H18BrF2NO4: C, 51.60; H, 4.10; N, 3.17. Found C, 51.65; H, 4.19; N, 3.10.

Provenance & Evidence