Step 1: Synthesis of ethyl 1H-benzimidazole-4-carboxylate
2.50 g (15.4 mmol) of 1H-benzimidazole-4-carboxylic acid was dissolved in 100 mL of ethanol, 50 mL of saturated ethanolic hydrochloric acid solution was added, and heated and refluxed for 15 hours. After the reaction was completed, the reaction mixture was slowly poured into saturated aqueous potassium carbonate solution and extracted with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate and subsequently concentrated to about 50 mL by rotary evaporator and filtered to obtain the product. 1.80 g (9.46 mmol, 61% yield) of ethyl 1H-benzimidazole-4-carboxylate was finally obtained as a colorless solid. Thin layer chromatography (TLC) analysis showed an Rf value of 0.92 [silica gel plate, unfolding agent dichloromethane/methanol (80/20)]. Mass spectrometry (MS) analysis showed [ESI (M + H)+]] = 191.
