In a 22 L three-necked flask equipped with a reflux condenser tube, a nitrogen introduction tube and a mechanical stirrer, sodium ethoxide (360 g, 5.29 mol), toluene (4 L), ethanol (18 mL, 0.265 mol) and ethyl acetate (1.04 L, 10.6 mol) were added sequentially and stirring was initiated. After stirring for 1 h, the reaction mixture was warmed up to 26 °C. Subsequently, ethyl 2-pyridinecarboxylate (Fluka; 400 g, 2.65 mol) was added to the reaction system and the mixture was heated to reflux (90 °C) and maintained for 18 hours. After completion of the reaction, the mixture was cooled to room temperature, diluted with toluene (8 L) and subsequently washed with deionized water (6 L) and partitioned. The aqueous layer was adjusted to pH 5 with glacial acetic acid and extracted with ethyl acetate (2 x 4 L). The organic layers were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford 466 g (91% yield) of the target product ethyl 3-oxo-3-(2-pyridinyl)propionate as a dark-colored oil, with a purity of 93% by HPLC analysis. Mass spectrum (ES+) m/e: 194 ([M+H]+).
