Dimethyl Sulfate → 1-Chloro-2-methoxy-4-methylbenzene

Participants

Reaction Steps

To a solution of 2-chloro-5-methylphenol (10) (250 g, 1.75 mol) in CH3N (2.5 L) was added Me2SO4 (184 mL, 1.93 mol) and K2CO3 (314 g, 2.28 mol). The reaction mixture was heated to reflux for 6 h with mechanical stirring. The reaction mixture was cooled to ambient temperature and filtered through Celite. The filtrate was evaporated. The residue was diluted with EtOAc (1.5 L), washed with water (1.5 L*2) and brine (1.5 L) successively, dried over MgSO4, filtered and concentrated under reduced pressure to give 2-chloro-5-methylanisole (11) as a light yellow oil (274 g, quantitative). 1H NMR (400 MHz, CDCl3): δ 7.20-7.25 (d, 1H), 6.73 (s, 1H), 6.68-6.71 (d, 1H), 3.86 (s, 3H), 2.31 (s, 3H).

Provenance & Evidence