The general procedure for the synthesis of 2-bromo-3-fluorobenzoic acid from 2-amino-3-fluorobenzoic acid is as follows: in a 1L three-necked round-bottomed flask equipped with a dropping funnel and a thermometer, 20g (0.13 mol) of 2-amino-3-fluorobenzoic acid and 160mL of acetonitrile were added. After the mixture was cooled to 0 °C, 160 mL of 47% hydrobromic acid solution was added slowly and dropwise over 10 min. Subsequently, a solution prepared from 10 g (0.145 mol) of sodium nitrite (NaNO2) dissolved in 20 mL of water was added dropwise to the reaction system over 1 hour. After the dropwise addition, the reaction mixture was continued to be stirred at 0°C for 5 min. Next, 21.8 g (0.15 mol) of copper bromide (CuBr) was added in batches over 30 minutes. The reaction mixture was transferred to a 70°C oil bath and stirred continuously for 1 hour. Upon completion of the reaction, the mixture was cooled to 0 °C, diluted with 700 mL of water and the precipitate was collected by filtration. The precipitate was washed with cold water and dried under vacuum to give the orange solid product 2-bromo-3-fluorobenzoic acid in a yield of 22 g and 78%.
