2-Methyl-4-nitrophenol → 1-(Difluoromethoxy)-2-methyl-4-nitrobenzene

Participants

Reaction Steps

To a solution of 2-methyl-4-nitrophenol (14 g, 91.50 mmol) in dimethylformamide (120 mL) and water (25 mL) was added Cs2CO3 (41.8 g, 128.22 mmol), and sodium 2-chloro-2,2-difluoroacetate (32 g, 209.84 mmol). The resulting solution was stirred for 20 minutes at room temperature, then for an additional 3 hours at 100° C. The reaction solution was cooled to room temperature before the addition of 100 ml of H2O. The resulting solution was extracted with EtOAc (4×100 ml) and the combined organic layers were washed with H2O (2×150 mL), dried over Na2SO4, concentrated in vacuo. The residue was purified by silica gel column chromatography to provide 16 g (86%) of 1-(difluoromethoxy)-2-methyl-4-nitrobenzene.

Provenance & Evidence