Example 7A Synthesis of ethyl 4-bromothiophene-2-carboxylate: 663 mg (3.20 mmol) of 4-bromothiophene-2-carboxylic acid (the compound of Example 6A) was dissolved in 25 mL of ethanol and 0.1 mL of concentrated sulfuric acid was added as a catalyst. The reaction mixture was heated to reflux and kept reacting overnight. Upon completion of the reaction, the mixture was cooled to room temperature, followed by the addition of saturated aqueous sodium bicarbonate solution to neutralize the reaction system. The mixture was diluted with water and extracted with ethyl acetate. The organic phases were combined, dried with anhydrous sodium sulfate, filtered to remove the desiccant and the filtrate was concentrated under reduced pressure. After the above steps, 700 mg of the target product ethyl 4-bromo-2-thiophenecarboxylate was obtained in 89% yield of the theoretical value. The structure of the product was confirmed by 1H-NMR (400 MHz, DMSO-d6): δ= 8.07 (d, 1H), 7.78 (d, 1H), 4.30 (q, 2H), 1.30 (t, 3H). GC-MS analysis (Method 11) showed: retention time Rt = 4.69 min; mass spectrum (EIpos): m/z = 234 [M]+.
