General procedure for the synthesis of 5-bromo-4-chlorothiophene-2-carboxylic acid from 1-(5-bromo-4-chlorothiophene-2-yl)ethanone: 1-(5-bromo-4-chlorothiophene-2-yl)ethanone (3.4 g, 14.3 mmol) was dissolved in a 1N NaOH solution (200 mL) at 0 °C, and bromine (Br2, 2.4 mL, 47.1 mmol) was slowly added dropwise. After 12 hours of reaction, the basic solution was extracted with dichloromethane (DCM). The aqueous phase was adjusted to pH 1 with hydrochloric acid and extracted several times with DCM. The organic phases were combined, dried with anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to give 5-bromo-4-chlorothiophene-2-carboxylic acid (1.5 g, 44% yield) as a white powder.
