Citric Acid → Ethyl 3-(4-pyridyl)-3-oxopropionate

Participants

Reaction Steps

To a solution of 4-pyridinecarboxylic acid (50.0 g, 406 mmol) in tetrahydrofuran (250 ml) was added 1,1′-carbonylbis-1H-imidazole (72.5 g, 447 mmol), and the mixture was stirred at room temperature for 30 min. To the reaction solution was added monoethyl malonate magnesium salt (82.9 g, 487 mmol), and the mixture was heated under reflux for 30 min. To the reaction solution were added ethyl acetate (200 ml) and water (200 ml), and citric acid was added until the pH of the aqueous layer became 7. The reaction solution was extracted with ethyl acetate (400 ml×2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was washed with diisopropyl ether-hexane and recrystallized from diisopropyl ether-hexane to give ethyl 3-oxo-3-(4-pyridyl)propionate (13.3 g, 17%).

Provenance & Evidence