Synthesis
Urea (19.39 g, 0.32 mol, JT Baker) was slowly added to fuming sulfuric acid (26-29.5% free SO3, 135 mL, 2.65 mol, Aldrich) under cooling in an ice-water bath over a period of 20 min, and the reaction temperature was controlled to be maintained at 8 to 15°C. After stirring for 30 min, ethyl 2-formylbutyrate was added dropwise over 18 min ( 46.55 g, 0.32 mol, from Example LC), keeping the reaction temperature constant. After continued stirring for 30 minutes, a second portion of urea (15.07 g, 0.25 mol) was added over 10 minutes at the same temperature. Subsequently, the reaction mixture was stirred at room temperature for 65 hours and then heated at 90-100°C for 2 hours (gas was observed to escape, the reaction was exothermic, and the temperature rose to 110°C). Upon completion of the reaction, the mixture was cooled to 30 °C using an ice water bath and ice (270 g) was slowly added to ensure that the temperature did not exceed 35 °C. The mixture was further cooled to 5 °C and stirred for 20 min. The precipitated solid was collected by filtration, washed sequentially with cold water, hexane and ether and dried by filtration to give 5-ethyluracil in 38.85 g (85.9%) yield.
