Synthesis
Step 1. Urea (12 g, 200 mmol) was added to an ethanol solution (300 mL) of sodium ethoxide pre-prepared from sodium metal (5.52 g, 240 mmol, 1.2 equiv). Diethyl 2-(ethoxymethylene)malonate (43.2 g, 200 mmol, 1.0 eq.) was then added and the reaction mixture was stirred at 20 °C for 24 h. The reaction mixture was then warmed up to 90 °C and continued to be stirred for 24 h. The reaction mixture was then stirred at 20 °C for 24 h. Upon completion of the reaction, ethanol was removed by distillation under reduced pressure. Ice water (100 mL) was added to the residue to dissolve the solid. The product was precipitated by dropwise addition of cold dilute hydrochloric acid. The solid was collected by filtration to afford ethyl 2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (8.5 g, 23% yield), which could be used in subsequent steps without further purification.
