Synthesis
A. Pre-preparation of 2-bromo-1-(methoxymethoxy)-4-methylbenzene. 2-Bromo-4-methylphenol (13.1 g, 70.0 mmol), dimethoxymethane (35 mL), p-toluenesulfonic acid (100 mg), and dichloromethane (300 mL) were placed in a nitrogen-protected reaction setup assembled with a Soxhlet condenser containing activated 3A molecular sieves and heated to reflux for three days. Freshly activated molecular sieves were replaced every 24 hours. After completion of the reaction, the reaction mixture was cooled and volatiles were removed by rotary evaporator. The residue was dissolved in 100 mL of ether and washed sequentially with 100 mL of 2 M sodium hydroxide solution, 100 mL of water and 100 mL of brine. The organic layer was dried with anhydrous magnesium sulfate and filtered through a short column of silica gel. The solvent was removed under reduced pressure to give 14.5 g (92% yield) of 2-bromo-1-(methoxymethoxy)-4-methylbenzene as a light yellow oil, which was used directly in the next reaction.1H NMR (CDCl3) δ 7.40 (m, 1H), 7.07 (m, 2H), 5.25 (s, 2H), 3.55 (s, 3H), 2.31 (s, 3H).
