A-6 Synthesis of ethyl 5-formyl-1H-pyrrole-2-carboxylate and ethyl 4-formyl-1H-pyrrole-2-carboxylate Procedure: 75 mL of dichloromethane solution of phosphorus trichloride (25 mL, 0.27 mol) was slowly added to 75 mL of dichloroethane solution of N,N-dimethylformamide (21 mL, 0.27 mol) at 0 °C. The reaction mixture was stirred at room temperature for 30 minutes and then cooled to 0°C again. Subsequently, a solution of ethyl pyrrole-2-carboxylate (25 g, 0.18 mol) dissolved in 50 mL of dichloroethane was slowly added dropwise. After the dropwise addition was completed, the reaction mixture was stirred at room temperature for 30 minutes and then continued stirring at 40 °C for 1 hour. After completion of the reaction, the mixture was carefully poured into ice water and the pH was adjusted to 11 with 5N sodium hydroxide solution.The reaction mixture was extracted with ethyl acetate, the organic phases were combined, washed sequentially with water and saturated saline, and finally dried with anhydrous sodium sulfate. Separation by column chromatography (eluent ratio 1:3 ethyl acetate:hexane) gave 15 g (50% yield) of ethyl 5-formyl-1H-pyrrole-2-carboxylate and 2 g (7% yield) of ethyl 4-formyl-1H-pyrrole-2-carboxylate. The products were confirmed by 1H-NMR (300 MHz, dimethylsulfoxide-d6) and mass spectrometry: 1H-NMR δ 13.02 (br s, 1H, NH), 9.69 (s, 1H, CHO), 6.95 (d, 1H), 6.86 (d, 1H), 4.27 (q, 2H, CH2), 1.28 (t, 3H, CH3). ms m/z 167 [M+].
