The general procedure for the synthesis of 3-fluoro-4-methoxybenzyl bromide from (3-fluoro-4-methoxyphenyl)methanol was as follows: at room temperature, (3-fluoro-4-methoxyphenyl)methanol (2.35 g, 15.05 mmol) and triethylamine (3.15 mL, 22.58 mmol) were dissolved in anhydrous dichloromethane (50 mL). Subsequently, methanesulfonyl chloride (1.41 mL, 18.06 mmol) was added dropwise. After 15 minutes of reaction, the reaction mixture was diluted with dichloromethane (50 mL) and the organic layer was washed with saturated aqueous sodium bicarbonate solution. The organic layer was separated, dried with anhydrous sodium sulfate and concentrated under reduced pressure. The residue was dissolved in anhydrous acetone (100 mL), excess lithium bromide was added and the mixture was heated to reflux for 30 minutes. After the reaction was complete, the solution was cooled and the solvent was evaporated under reduced pressure. The residue was partitioned between ethyl acetate and water and the aqueous layer was extracted twice with ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford the target product 3-fluoro-4-methoxybenzyl bromide (3.00 g, 91% yield). The structure of the product was confirmed by 1H NMR (CDCl3): δ7.16-7.07 (2H, m), 6.90 (1H, dd, J=8.3,8.4Hz), 4.45 (2H, s), 3.89 (3H, s).
