Step a) Synthesis of the intermediate 2-(ethoxymethylene)-3-oxobutanoic acid ethyl ester: A mixed solution of ethyl acetoacetate (20 g, 154 mmol), triethyl orthoformate (51.1 mL, 307 mmol) and acetic anhydride (43.5 mL, 461 mmol) was heated and reacted for 5 hrs at 130 °C. After completion of the reaction, the mixture was cooled to room temperature. Subsequently, excess triethyl orthoformate and acetic anhydride were removed by concentration under reduced pressure. The residual acetic anhydride and triethyl orthoformate were further removed by distillation under reduced pressure (30 mbar, 30-70°C). Finally, the target product ethyl 2-(ethoxymethylene)-3-oxobutanoate was purified by distillation (6 mbar, 80 °C to 128 °C) as a viscous yellow oil (22.8 g, 80% yield). The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3): δ 7.59-7.69 (m, 1H), 4.17-4.34 (m, 4H), 2.29-2.44 (m, 3H), 1.25-1.44 (m, 6H).
