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

Temperature

100 °C

diacetoxypalladium (3.13 mg, 0.01 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (125 mg, 0.35 mmol), 1-bromo-3,5-difluorobenzene (0.044 ml, 0.38 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (17.15 mg, 0.03 mmol) and cesium carbonate (170 mg, 0.52 mmol) dissolved in 1,4-dioxane (2 ml). The resulting suspension was degased with argon and then stirred at 100 °C for 10 hours. The reaction mixture was allowed to cool to room temperature. The reaction mixture was quenched with water and extracted with dichloromethane (2 x 10 ml). The combined organic phases were dried over magnesium sulfate and concentrated to afford the crude product as a orange/yellow oil. The crude product was purified by flash chromatography on silica gel eluting with 0 to 10% methanol in dichloromethane. 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 (118 mg, 71.9 %) as a yellow gum.

ORD record

ord-49d23b5c1f9b4ddcb11fd7200ac09018

Source dataset

750 AstraZeneca ELN dataset

Original link

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