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

Pd complexe (142 mg, 0.16 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (577 mg, 1.61 mmol), 1-bromo-3,5-difluorobenzene (0.232 ml, 2.01 mmol) and cesium carbonate (787 mg, 2.41 mmol) dissolved in 1,4-dioxane (12 ml). The resulting suspension was degased with argon and then stirred at 100 °C (10:30). After 3 hours, lcms showed complete reaction. The reaction mixture was allowed to cool to room temperature, filtered and concentrated. The crude product was 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 (315 mg, 41.6 %) as a clear yellow foam. **low yield but LCMS of the crude showed complete reaction!** LCMS and NMR are OK

Provenance & Evidence