Synthesis
The reaction was carried out with 4-bromo-3,5-dimethylphenol (25.0 g, 124.3 mmol), iodomethane (35.3 g, 248.6 mmol), and potassium carbonate (34.4 g, 248.6 mmol) in 62.5 mL of DMF with stirring at room temperature for 2 hours. After completion of the reaction, the mixture was diluted with 300 mL of ether and washed sequentially with 250 mL of water and 5 x 100 mL of brine. The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated to give the crude product. Purification by fast column chromatography (silica gel, 90:10 hexane/ethyl acetate) afforded 4-bromo-3,5-dimethylanisole (26 g, 120.8 mmol, 97% yield).1H NMR (CDCl3) δ: 2.39 (s, 6H), 3.76 (s, 3H), 6.67 (s, 2H).
References
[1] Patent: WO2014/128198, 2014, A1. Location in patent: Page/Page column 44-45
[2] Organic Letters, 2005, vol. 7, # 17, p. 3721 - 3724
[3] Journal of the American Chemical Society, 2007, vol. 129, # 11, p. 3267 - 3286
[4] Angewandte Chemie - International Edition, 2013, vol. 52, # 50, p. 13405 - 13409
[5] Angew. Chem., 2013, vol. 125, # 50, p. 13647 - 13651,5
