Ethyl 4H-thieno[2,3-d]pyrrole-5-carboxylate

98-03-3

637-81-0

46193-76-4

GENERAL METHOD: Sodium ethoxide (8.17 g, 120 mmol, 20 wt% ethanol solution) was slowly added dropwise to an anhydrous ethanol (50 mL) mixture of 2-thiophenecarboxaldehyde (2.8 mL, 30 mmol) and ethyl azidoacetate (15.4 g, 120 mmol) at -10 °C. After dropwise addition, the reaction mixture was stirred at room temperature for 4 hours. Subsequently, the reaction was quenched by addition of excess saturated aqueous ammonium chloride solution. The mixture was extracted with ethyl acetate (2 x 80 mL), and the organic layers were combined, washed with saturated saline (2 x 60 mL) and dried over anhydrous sodium sulfate. After removing the solvent by evaporation under reduced pressure, the residue was dissolved in toluene (30 mL) and heated to reflux for 1 hour. After completion of the reaction, it was cooled to room temperature and the solvent was removed by evaporation. The residue was purified by column chromatography (eluent: n-hexane/dichloromethane=2:1) to afford ethyl 4H-thieno[3,2-b]pyrrole-5-carboxylate (4a) as a white solid (2.93 g, 50% yield). The product was characterized by 1H NMR (400 MHz, CDCl3) and 13C NMR (100 MHz, CDCl3) with the following data: 1H NMR δ 9.26 (br s, 1H), 7.32 (d, J = 5.2 Hz, 1H), 7.14 (d, J = 0.8 Hz, 1H), 6.96 (dd, J = 5.2, 0.8 Hz, 1H ), 4.38 (q, J = 7.6 Hz, 2H), 1.39 (t, J = 7.6 Hz, 3H); 13C NMR δ 161.7, 141.3, 129.4, 127.1, 124.8, 111.1, 107.5, 60.7, 14.5.