91-16-7

5424-43-1

To a stirred solution of N,N,N',N'-tetramethylethylenediamine (TMEDA, 5.43 mL, 36.19 mmol, 1.0 eq.) in anhydrous ethyl ether (Et2O, 100 mL) was slowly added n-butyllithium (n-BuLi, 22.6 mL, 36.19 mmol, 1.0 eq., 1.6 M hexane solution) at room temperature. The mixture was stirred for 10 minutes and then 1,2-dimethoxybenzene (5.0 g, 36.19 mmol) was added. The reaction mixture was continued to be stirred at room temperature for 2.5 h. The reaction mixture was then cooled to -78 °C and a solution of anhydrous hexane (10 mL) with bromine (Br2, 1.85 mL, 36.19 mmol, 1.0 equiv) was added dropwise. The reaction was kept at -78 °C for 30 min, after which it was slowly warmed to room temperature. Upon completion of the reaction, the reaction was quenched with saturated aqueous sodium sulfite (Na2SO3, 20 mL). The reaction mixture was extracted with ethyl acetate (EtOAc, 3 × 30 mL), the organic layers were combined and washed sequentially with water and brine, dried with anhydrous sodium sulfite (Na2SO4) and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with the eluent of petroleum ether/ethyl acetate (9.5:0.5 to 9:1) to afford 1-bromo-2,3-dimethoxybenzene (6.68 g, 85% yield) as a colorless oil.