The general procedure for the synthesis of 2-bromo-4-phenylpyridine from 4-phenylpyridine was as follows: dimethylaminoethanol (DMAE, 1.50 mL, 15.0 mmol) was dissolved in hexane (20.0 mL) and stirred under cooling in an ice bath. Under the same cooling conditions, n-butyllithium (2.5 mol/L hexane solution, 12.0 mL, 30.0 mmol) was slowly added dropwise, followed by stirring the reaction mixture for 30 minutes. Keeping the ice bath cool, a hexane solution (30.0 mL) of 4-phenylpyridine (776 mg, 5.00 mmol) was slowly added and stirring was continued for 1 h under these conditions. The reaction system was cooled to -78°C, a hexane solution (15.0 mL) of carbon tetrafluoride (6.30 g, 18.0 mmol) was slowly added dropwise and stirred for 50 minutes. Upon completion of the reaction, deionized water was added under cooling in an ice bath to quench the reaction, followed by extraction with ethyl acetate (100 mL x 2). The organic layers were combined, washed with saturated sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure and the residue was purified by silica gel column chromatography using ethyl acetate/hexane (1:4, v/v) as eluent to afford the target product 2-bromo-4-phenylpyridine (645 mg, 55.1% yield).
