General procedure for the synthesis of ethyl 2-bromo-5-fluorobenzoate from ethyl m-fluorobenzoate: in a 100 mL round-bottomed flask, ethyl m-fluorobenzoate (1.68 g, 1.0 eq.), N-bromosuccinimide (NBS, 1.87 g, 1.05 eq.), palladium acetate (Pd(OAc)2, 78.5 mg, 0.035 eq.) and sodium persulfate ( Na2S2O8, 2.86 g, 1.2 eq.) were dissolved in 12 mL of commercially available dichloroethane. Subsequently, trifluoromethanesulfonic acid (TfOH, 2.2 mL, 2.5 eq.) was added to the reaction solution. The reaction mixture was stirred at 80°C for 9 hours. Upon completion of the reaction, the mixture was cooled to room temperature and saturated sodium bicarbonate (NaHCO3) solution was added to quench the reaction. The reaction mixture was diluted with dichloromethane and washed once with saturated aqueous NaHCO3 solution. The organic layer was dried with anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure. Finally, the residue was purified by silica gel column chromatography to afford the target product ethyl 2-bromo-5-fluorobenzoate (1.71 g) in 70% yield.
