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 (0.033 g, 0.15 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (1.326 g, 3.7 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.182 g, 0.31 mmol), 1-bromo-3,5-difluorobenzene (0.533 ml, 4.63 mmol) and cesium carbonate (1.808 g, 5.55 mmol) suspended in 1,4-dioxane (36 ml). The resulting suspension was degased with argon and then stirred at 100 °C over the WE (66hours). Albeit Lcms showed ~ 7% SM remaining, the reaction was stopped. The reaction mixture was allowed to cool to room temperature, the insolubles were removed by filtration and the filtrate concentrated. The crude product was adsorbed on silica gel and purified by flash chromatography on silica gel eluting with 2 to 5% 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 (1.172 g, 67.3 %) as a beige foam.

Provenance & Evidence