The general procedure for the synthesis of 4-bromo-2,6-di-tert-butyl anisole from 4-bromo-2,6-di-tert-butylphenol and dimethyl sulfate was as follows: 4-bromo-2,6-di-tert-butylphenol (50 g, 0.175 mol) and potassium carbonate (96.7 g, 4.0 eq.) were dissolved in acetone (750 mL) under argon atmosphere protection. Dimethyl sulfate (38.6 g, 1.75 eq.) was slowly added to the reaction system at 22 °C, followed by heating the reaction mixture to reflux and stirring for 13 hours. After completion of the reaction, the insoluble material was removed by filtration and the solvent was evaporated under reduced pressure. A partition extraction was performed by adding ethyl acetate (150 mL) and water (100 mL) to the residue. The organic layer was washed sequentially with water (100 mL), 5% aqueous NaHCO3 (100 mL) and 5% aqueous NaCl (100 mL). The organic layer was dried with anhydrous magnesium sulfate, and after filtration by gravity, the filtrate was concentrated under reduced pressure to afford 4-bromo-2,6-di-tert-butylanisole (56.1 g, brown oil) in 95.2% yield. The product was analyzed by 1H-NMR (300 MHz, CDCl3, TMS) with chemical shifts of δ 1.41 (s, 18H), 3.68 (s, 3H), 7.33 (s, 2H).
