General procedure for the synthesis of methyl 2-bromothiophene-3-carboxylate from methanol and 2-bromo-3-thiophenecarboxylic acid: 2-bromo-3-thiophenecarboxylic acid (10.1 g, 49 mmol) was dissolved in methanol (100 mL) and sulfuric acid (2.5 mL, 45 mmol) was added as a catalyst. The reaction mixture was heated to reflux and kept reacting overnight. Upon completion of the reaction, most of the methanol was removed by distillation under reduced pressure. The concentrated mixture was slowly poured into pre-cooled ice water. The product in the aqueous phase was extracted with ethyl acetate (EtOAc). The organic phases were combined and washed sequentially with water and saturated aqueous sodium bicarbonate. The organic phases were dried with anhydrous sodium sulfate, and after filtration to remove the desiccant, the filtrate was concentrated under reduced pressure to afford the target product methyl 2-bromothiophene-3-carboxylate 10.77 g (100% yield). The product was characterized by 1H NMR (400.15 MHz, DMSO-d6): δ 7.65 (d, J = 6Hz, 1H), 7.34 (d, J = 6Hz, 1H), 3.78 (s, 3H).
