2-Bromopyridine → Ethyl difluoro(pyridin-2-yl)acetate

Participants

Reaction Conditions

Reaction Steps

To the solution of 2-bromopyridine (18 mL, 0.2 mmol) and ethyl bromodifluoroacetate (27 g, 0.22 mol) in DMSO (70 mL) was added copper powder (29 g, 0.46 mol). The mixture was stirred at 50° C. for 4 h. After cooling to room temperature, the reaction mixture was diluted with isopropyl acetate (100 mL). A solution of potassium dihydrogen phosphate (1.27 M, 150 mL) was added and stirred for 30 min. the copper salt was removed by filtration and washed with isopropyl acetate (100 mL). The filtrate layer was separated. The organic layer was washed with water (2×100 mL) and dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 5%-40% methyl t-butyl ether in hexanes in 40 min) afforded difluoro-pyridin-2-yl-acetic acid ethyl ester (27 g, 68%) as a colorless oil. LC-MS m/e 202 (MH+).

Provenance & Evidence