Synthesis
The general procedure for the synthesis of ethyl 2-aminothiophene-3-carboxylate from 1,4-dithio-2,5-diol and ethyl cyanoacetate was as follows: in a 2-5 mL microwave reaction flask, ethyl cyanoacetate (0.22 mmol, 1.0 equiv.) and trifluoroethanol (2 mL) were added, and stirred for 2 min until complete dissolution. Subsequently, 1,4-dithio-2,5-diol (0.11 mmol, 0.5 eq.) was added and stirring was continued for 5 min. Next, triethylamine (0.242 mmol, 1.1 eq.) was added and the reaction mixture was stirred for another 2 minutes. The reaction flask was sealed and placed in a microwave reactor and heated at 60 °C for 390 min. After completion of the reaction, the solvent was removed by vacuum evaporation. The crude product was purified by silica gel fast column chromatography (eluent: ethyl acetate/hexane mixed solvent) to afford the target product ethyl 2-aminothiophene-3-carboxylate.
References
[1] Synthesis (Germany), 2013, vol. 45, # 1, p. 45 - 52
[2] Journal of Medicinal Chemistry, 1999, vol. 42, # 26, p. 5437 - 5447
[3] Beilstein Journal of Organic Chemistry, 2015, vol. 11, p. 875 - 883
[4] Chemical Communications, 2013, vol. 49, # 2, p. 190 - 192
[5] Archiv der Pharmazie, 2011, vol. 344, # 7, p. 459 - 465
