The general procedure for the synthesis of 3,5-dichloro-4-fluorobromobenzene from 3-chloro-4-fluorobromobenzene was as follows: to a dry Schlenk flask equipped with a magnetic stirrer and septum under argon protection was added 20 mL of freshly titrated iPrMgCl-LiCl (1.24 M, THF solution, 1.0 equiv.), followed by a slow dropwise addition of 3.8 mL of diisopropylamine (1.1 equiv.) ). The reaction mixture was stirred at room temperature until complete gas release (~48 hours). The precipitate formed was dissolved with additional dry THF. A fresh solution of iPr2NMgCl-LiCl in THF was titrated at 25 °C using benzoic acid and 4-(phenylazo)diphenylamine as indicators, and the concentration was measured to be 0.59 M. 4-Bromo-2-chloro-1-fluorobenzene (0.209 g, 1.00 mmol) was dissolved in THF (1 mL) and iPr2NMgCl-LiCl (0.59 M , 3.39 mL, 2.00 mmol) solution was added and stirred at 25 °C for 15 min. Subsequently, hexachloro-2-acetone (0.397 g, 1.50 mmol) was added at 0 °C and stirring was continued for 15 min. The reaction mixture was quenched with saturated aqueous NaHCO3 solution, extracted with ethyl acetate and the organic phase was dried over anhydrous Na2SO4. After filtration, the solvent was concentrated under reduced pressure. Quantitative GC analysis showed the ratio of 5-bromo-1,3-dichloro-2-fluorobenzene to the regional isomers to be about 12:1. Purification by fast column chromatography (silica gel, n-hexane) afforded 5-bromo-1,3-dichloro-2-fluorobenzene (0.190 g) as a colorless oil.
