(1) In a 20 liter autoclave, 1 kg ethyl 5-amino-4-cyano-3-(2-ethoxy-2-carboxymethyl)-2-thiophenecarboxylate, 12 liters of tetrahydrofuran, 1.92 kg potassium carbonate, 2.3 kg ethyl bromoacetate, and 20 grams of crown ether were added and heated to reflux, and the progress of the reaction was monitored by high-performance liquid chromatography (HPLC) (Fig. 9 shows the end of the reaction by HPLC). control plot), the reaction took about 3-4 hours to complete. After completion of the reaction, the mixture was filtered and the filtrate was concentrated by distillation under reduced pressure. Subsequently, 4 liters of ethanol were added and pulped under ice bath conditions for 3-4 hours and filtered again. The filter cake was washed with ice ethanol and finally dried in an oven at 45°C to obtain 1.25 kg of ethyl 5-[bis(2-ethoxy-2-carboxymethyl)amino-]-4-cyano-3-(2-ethoxy-2-carboxymethyl)-2-thiophene carboxylate in 91% yield and 99.86% purity.
