Methane, dichloromethoxy- → 2,4-Difluoro-6-methoxybenzaldehyde

Participants

Reaction Steps

3,5-Difluoroanisole (50 g, 0.35 mol) was charged to a 3-neck flask fitted with thermometer, dropping funnel and argon bubbler. Dichloromethane (200 mL) was added and the solution was cooled in ice-water. Titanium (IV) chloride (61.5 mL, 0.56 mol) was added dropwise (15 min), followed by dropwise addition of α,α-dichloromethyl methyl ether (31.5 mL, 0.35 mol) so that the temperature was maintained <10° C. (approx 20 min). The reaction was stirred in ice-water for a further 140 min, poured into ice-water (1 L), then extracted thrice with DCM. The organic solutions were washed with water, brine then dried (MgSO4) and evaporated. The crude product was purified using the Versaflash (80×300 mm SiO2 cartridge, gradient from DCM to 5% EtOAc) in 7 separate batches to give the title compound (34.5 g, 57%) as an orange solid.

Provenance & Evidence