Synthesis
General procedure for the synthesis of 4-bromomethyl-2-chloro-1-methoxybenzene from 2-chloro-1-methoxy-4-methylbenzene: 2-chloro-1-methoxy-4-methylbenzene (2.6 mL, 19.2 mmol) was dissolved in dichloromethane (30 mL) and N-bromosuccinimide (3.75 g, 21.1 mmol) and AIBN (36.0 mg). The reaction mixture was heated to reflux, kept for 19 h and then cooled to room temperature and filtered to remove the precipitate. The filtrate was diluted with dichloromethane and washed sequentially with 0.5 M aqueous sodium bicarbonate and water. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 4-bromomethyl-2-chloro-1-methoxybenzene (4.73 g, 82% yield). The crude product (benzyl bromide) could be used for subsequent reaction without further purification.1H NMR (400 MHz, CDCl3): δ 7.42 (d, 1H, J = 2.4 Hz), 7.26 (dd, 1H, J = 2.4 Hz, J = 8.4 Hz), 6.88 (d, 1H, J = 8.4 Hz), 4.44 (s, 2H), 3.90 (s. 3H).
References
[1] Patent: US2002/169174, 2002, A1
[2] European Journal of Organic Chemistry, 2005, # 2, p. 317 - 325
[3] Patent: WO2012/7868, 2012, A2. Location in patent: Page/Page column 94-95
[4] Patent: US2007/88053, 2007, A1. Location in patent: Page/Page column 19
