1-Bromo-3,5-difluorobenzene → methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate

Participants

Reaction Conditions

Reaction Steps

diacetoxypalladium (6.26 mg, 0.03 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (200 mg, 0.56 mmol), 1-bromo-3,5-difluorobenzene (0.080 ml, 0.70 mmol) and cesium carbonate (273 mg, 0.84 mmol) dissolved in 1,4-dioxane (8 ml). The resulting suspension was degased with argon and then stirred at 100 °C (18:00) for 15 hours. The reaction mixture was allowed to cool to room temperature, filtered and concentrated. The crude product was adsorbed on silica gel and purified by flash chromatography on silica gel eluting with 0 to 6% methanol in ethyl acetate. The solvent was evaporated to dryness to afford methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (173 mg, 65.9 %) as a clear yellow foam. LCMS and NMR are OK.

Provenance & Evidence