General procedure for the synthesis of ethyl 5-methylthiazole-4-carboxylate from ethyl 2-amino-5-methylthiazole-4-carboxylate: ethyl 2-amino-5-methylthiazole-4-carboxylate (62.9 g, 338 mmol) was mixed with tetrahydrofuran (THF, 630 mL) in a three-necked round-bottomed flask equipped with a stirrer. The reaction mixture was heated to reflux followed by slow dropwise addition of isoamyl cyanide (52.6 g, 60.1 mL, 449 mmol). After the dropwise addition was completed, the reaction mixture was continued to be stirred under reflux conditions for 1 hour. Upon completion of the reaction, the reaction mixture was concentrated using a rotary evaporator (under high vacuum) to give 70 g of crude product, which appeared as a thick orange oil. Purification of the crude product by silica gel column chromatography (silica gel 400 g, eluent 20-45% ethyl acetate/hexane) gave 39.47 g (68% yield) of ethyl 5-methylthiazole-4-carboxylate as a yellow solid. It was analyzed by liquid chromatography-electrospray mass spectrometry (LC-ES/MS) and m/z 172 ([M+1]+) was measured with a retention time (TR) of 1.5 min.
