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 (0.439 g, 1.95 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (14 g, 39.06 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (2.260 g, 3.91 mmol), 1-bromo-3,5-difluorobenzene (5.62 ml, 48.83 mmol) and cesium carbonate (19.09 g, 58.60 mmol) suspended in 1,4-dioxane (250 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 16 hours. The reaction mixture was allowed to cool to room temperature, concentrated in presence of silica gel and purified by Chromatography on silica gel (Novasep) eluting with 0 to 10% 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 (10.30 g, 56.0 %) as an yellow foam.

Provenance & Evidence