Potassium Carbonate → 5-Bromo-2-(difluoromethoxy)pyrimidine

Participants

Reaction Conditions

Reaction Steps

A reaction vial was charged with 5-bromopyrimidin-2-ol (1.50 g, 8.57 mmol), sodium 2-chloro-2,2-difluoroacetate (2.61 g, 17.14 mmol), potassium carbonate (2.1 equiv.) and DMF (10 mL). The resulting mixture was sparged with nitrogen for ˜5 min., then heated to 65° C. and stirred overnight (˜15 h). After cooling to rt, the resulting mixture was partitioned between EtOAc (300 mL) and water (100 mL). The layers were separated and the organic portion was washed with water (50 mL×2) then 80 mL of hexanes was added and washed again with water (50 mL×2), brine, then dried over sodium sulfate. The resulting solution was filtered and concentrated to remove solvent which afforded a colorless oil as the crude product mixture. This material was purified by ISCO silica gel chromatography (gradient Hex/EtOAc mixtures as eluant; 40 g column) Fractions containing the desired product were collected, combined and concentrated under vacuum to afford 186 mg (10%) of a colorless oil as the title compound. 1H NMR (400 MHz, METHANOL-d4) δ 8.95-8.71 (m, 2H), 7.83-7.27 (m, 1H).

Provenance & Evidence