The general procedure for the synthesis of ethyl 2-amino-4-methyloxazole-5-carboxylate from ethyl acetoacetate and urea is as follows: ethyl acetoacetate (1 g, 6.07 mmol) was dissolved in acetonitrile (10 ml), hydroxy-toluenesulfonatooxy iodobenzene (2.85 g, 7.28 mmol, 1.2 eq.) was added, and the reaction mixture was stirred for about 20 min at room temperature (ca. 25° C). . Subsequently, the reaction system was warmed to about 80°C and heating was continued for about 2 hours. After addition of urea (0.43 g, 7.28 mmol, 1.2 eq.), the reaction mixture was heated at about 80°C for about 16 hours. Upon completion of the reaction, the acetonitrile was removed by rotary evaporation. The organic phase was separated by partitioning the residue between 5% aqueous sodium bicarbonate solution and ethyl acetate. The combined organic phases were dried with anhydrous sodium sulfate and concentrated to give the crude product. The crude product was dissolved in 6N hydrochloric acid solution and extracted with ether. The aqueous phase was neutralized to pH neutral with solid sodium bicarbonate under cooling conditions in an ice bath, and the precipitated solid was collected by vacuum filtration to afford the target product ethyl 2-amino-4-methyloxazole-5-carboxylate (320 mg), which was shown by EIMS to be m/z 170.84 [M + H]+.
