Chloromethyl Methyl Ether → 1-Bromo-4-fluoro-2-(methoxymethoxy)benzene

Participants

Reaction Conditions

Reaction Steps

2-Bromo-5-fluorophenol (30 g, 0.16 mol) is dissolved in dichloromethane (170 mL) and cooled to 0° C. To this solution is added diisopropylethylamine (36 mL, 0.20 mol) via syringe followed by chloromethyl methyl ether (16 mL, 0.20 mol) via an addition funnel. The solution is stirred and warmed to room temperature. After 2 h, the mixture is washed with saturated aqueous NH4Cl, water, and brine. The organic portion is dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (Biotage® Si65M, 20% AcOEt/hexane) to yield 26.1 g (71%) of the title compound as a clear colorless oil. 1H NMR 400 MHz (CDCl3) δ 7.46-7.53 (m, 1H), 6.92-6.99 (m, 1H), 6.63-6.70 (m, 1H), 5.26 (s, 2H), 3.55 (s, 3H).

Provenance & Evidence