Diethyl Malonate → 3-Quinolinecarboxylic acid, 1,2-dihydro-4-hydroxy-1-methyl-2-oxo-, ethyl ester

Participants

Reaction Steps

To a solution of diethyl malonate (68.0 g, 0.425 mol) in DMF (400 mL) was added sodium hydride (66% in oil, 10.8 g, 0.30 mol) under ice-cooling, and the mixture was stirred at the same temperature for 5 min and at room temperature for 15 min. N-Methylisatoic anhydride (50.8 g, 0.287 mol) was added to the obtained mixture by small portions, and the mixture was stirred at 120° C. for 3 hr. Diisopropyl ether (500 mL) was added to the reaction mixture, and the precipitated solid was collected by filtration and washed with diisopropyl ether. The obtained solid was suspended in a mixture of methanol (250 mL) and water (500 mL), 5N hydrochloric acid (60 mL) was added dropwise, and the mixture was extracted twice with ethyl acetate. The combined organic layer was washed with water, and concentrated under reduced pressure. The residue was washed with diisopropyl ether to give the title compound (41.4 g, 58%).

Provenance & Evidence