Synthesis
General procedure for the synthesis of ethyl 4-bromo-3-hydroxybenzoate from 4-bromo-3-hydroxybenzoic acid: 4-bromo-3-hydroxybenzoic acid (5.0 g, 0.023 mol) was dissolved in a solvent mixture of 150 mL of benzene and 5 mL of ethanol, and 1 mL of methanesulfonic acid (MeSO3H) was added as a catalyst. A Dean-Stark manifold was installed and the reaction mixture was heated to reflux for 10 hours to remove the water generated. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in dichloromethane (CH2Cl2) and washed sequentially with water, 5% sodium bicarbonate (NaHCO3) solution and saturated brine. The organic phase was dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (eluent: ethyl acetate/hexane) to afford the target product ethyl 4-bromo-3-hydroxybenzoate (5.1 g, 90% yield) as a white solid. The product was characterized by 1H NMR (300 MHz, CDCl3): δ1.39 (t, J=7.2 Hz, 3H), 4.37 (q, J=7.2 Hz, 2H), 5.75 (s, 1H), 7.48 (d, J=8.1 Hz, 1H), 7.55 (d, J=8.1 Hz, 1H), 7.68 (s, 1H).
