Acetonitrile → 1-Bromo-4-methoxy-2-phenylmethoxybenzene

Participants

Reaction Steps

A 12 L four-necked round-bottomed flask equipped with mechanical stirrer, thermometer and reflux condenser with nitrogen inlet was charged with 2-bromo-5-methoxyphenol (615 g, 2.98 mol), CH3CN (6 L), K2CO3 (671 g, 4.77 mol), benzyl chloride (363 mL, 3.14 mol), and KI (6 g, 0.036 mol). The mixture was heated to reflux for 3 h, cooled to room temperature, and H2O (3 L) added to form a biphasic mixture. The aqueous layer was separated, CH3CN (3 L) removed in vacuo and EtOAc (4 L) added to extract the product. After a wash with H2O (3 L) and 10% NaCl solution (1.8 L), the organic layer was concentrated to dryness to afford 1-bromo-4-methoxy-2-(phenylmethoxy)benzene as a light yellow oil (895.5 g, 99%): bp 110° C. (2.5 mm Hg); 1H NMR δ 7.55-7.25 (m, 6 H), 6.55 (d, J=2.7 Hz, 1 H), 6.35 (dd, J=8.5 Hz, 1.5 Hz, 1 H), 5.1 (s, 2 H), 3.75 (s, 3 H).

Provenance & Evidence