反应详情

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.

1. customfitted with thermometer
2. temperaturewas maintained <10° C. (approx 20 min)
3. extractionextracted thrice with DCM
4. washThe organic solutions were washed with water, brine
5. dry with materialthen dried (MgSO4)
6. customevaporated
7. customThe crude product was purified
8. customseparate batches