Ethyl cyanoacetate (56.6 g, 0.5 mol), sulfur powder (16.0 g, 0.5 mol) and triethylamine (50.5 g, 0.5 mol) were added sequentially to a three-necked flask containing N,N-dimethylformamide (DMF, 100 mL) and stirred until completely dissolved. Subsequently, a solution of propionaldehyde (31.9 g, 0.55 mol) in acetaldehyde (15 mL) was added slowly and dropwise. During the reaction, the internal temperature was naturally increased to 60 °C and heated at this temperature with continuous stirring. Upon completion of the reaction, the reaction mixture was slowly poured into water and extracted with ethyl acetate. The organic phases were combined, washed sequentially with water and saturated saline, dried over anhydrous sodium sulfate, and the solvent was removed by distillation under reduced pressure. The resulting crude product was purified by silica gel column chromatography (MERCK Kiesel gel 60, eluent 20% ethyl acetate-hexane) to afford ethyl 2-amino-5-methylthiophene-3-carboxylate (81.8 g, 89% yield). The product was characterized by 1H-NMR (400 MHz, CDCl3): δ 1.33 (t, 3H, J = 7.2 Hz), 2.26 (d, 3H, J = 1.2 Hz), 4.25 (q, 2H, J = 7.2 Hz), 5.76 (br.s, 2H), 6.61 (q, 1H, J = 1.2 Hz).
