ethyl 2-bromo-5-ethoxy-4-methylbenzoate synthesis

Yield:-

Reaction Conditions:

with bromine in water;acetic acid at 60; for 1 h;

Steps:

4.A

To a solution of ethyl 5-ethoxy-4~methylbenzoate (500 mg, 2.40 mmol) in acetic acid (10 mL) and water (10 mL) in a 50 mL flask, bromine was added at room temperature. The resulting reaction mixture was stirred at 60 °C for 1 hour. After cooling to room temperature, the reaction mixture was diluted with 100 mL of hexanes: ether (80:20). The layers were separated and the organic layer was washed with saturated Na₂C0_3s brine, dried over Na₂S0₄, filtered and concentrated. The residue was purified on a silica gel column eluting with 5-10 % ethyl acetate in hexanes to yield the title compound 2-bromo-5-ethoxy-4-methylbenzoate as a light yellow solid. 1H NMR (CDC1₃, 500 MHz): δ 7.54 (d, J= 7.0 Hz, 1H), 7.47 (s, 1H), 7.17 (d, J- 7.51 Hz, 1H), 4.36 (q, 2H), 4.09 (q, 2H), 2.26 (s, 3H), 1.44 (t, J= 7.0 Hz, 3H), 1.38 (t, j= 7.50 Hz, 3H).

References:

WO2011/146324,2011,A1 Location in patent:Page/Page column 66; 67