8-Hydroxyquinoline → Ethyl 4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylate

Participants

Reaction Steps

DMF (9 L) and cesium carbonate (3.1 kg) were charged under nitrogen to a reactor and stirred for 10 min at room temperature. To this mixture, a solution of 8-hydroxyquinoline (0.275 kg) in DMF (1 L), copper iodide (0.27 kg) and 1-fluoro-4-iodobenzene (1.576 kg) were added under nitrogen. Then, ethyl 4-ethoxy-2-oxo-1,2-dihydropyridine-3-carboxylate (1 kg) was added and the reaction mixture was heated to 100° C. for 20 hrs under nitrogen. After completion of the reaction, the mixture was filtered through celite. To the filtrate, water (100 L) was added and the mixture was extracted three times with DCM (25 L). The combined DCM layers were washed two times with water (20 L), two times with 1.5 N HCl (5 L), and one time with brine (10 L), and then dried over sodium sulfate and concentrated to dryness. Petroleum ether (5 L) was added to the concentrate and the resulting slurry was stirred for 30 min. The solids were filtered and dried at room temperature in vacuum to give 1.1 kg crude ethyl 4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylate.

Provenance & Evidence