Synthesis
Starting with 2,3-dichloropropionitrile, the key intermediate methyl 3-amino-2-thiophene carboxylate was prepared, followed by diazotization and fluorination to prepare 2-Thiophenecarboxylicacid,3-fluoro-,methylester(9CI). The synthetic route is as follows: 
Figure 1 Synthetic route of 2-Thiophenecarboxylicacid,3-fluoro-,methylester(9CI)
Preparation of 2,3-dichloropropionitrile
Acrylonitrile and N,N-dimethylformamide were added to a 250mL four-necked flask equipped with a stirrer, thermometer, venting tube and condenser. The mixture was stirred and cooled to about 5℃. Chlorine gas was slowly introduced at a temperature of 5-10℃. When the amount of chlorine introduced was 120.0, the chlorine introduction was stopped. The reaction was maintained at 10-15℃ for 5 hours. Nitrogen gas was introduced to remove excess chlorine gas. The reaction was completed and the mixture was weighed to obtain 2,3-dichloropropionitrile. Preparation of methyl 2-mercaptoacetate: 2-Mercaptoacetic acid and methanol were added to a 500 mL four-necked flask equipped with a stirrer, thermometer, dropping funnel, and condenser. Concentrated sulfuric acid was added dropwise at 40 °C. After the addition was complete, the reaction was maintained at 35–40 °C for 8 hours. The mixture was allowed to stand and the water was separated to obtain the crude ester. The crude ester was then distilled under reduced pressure, and the fraction containing methyl 2-mercaptoacetate at 1333 Pa and 42–43 °C was collected. Preparation of methyl 3-amino-2-thiophenecarboxylate 200g of 28% sodium methoxide was added to a 500mL four-necked flask equipped with a stirrer, thermometer, dropping funnel and condenser. 53.8g of methyl 2-mercaptoacetate was added dropwise at 10-15℃. After the addition was completed, 100mL of methanol solution containing 65.0g of 2,3-dichloropropionitrile was added dropwise at 10-15℃. After the addition was completed, the reaction was kept at this temperature for 6 hours. Methanol was distilled off under reduced pressure. 200mL of cold water was added dropwise. The mixture was stirred, washed and filtered. The filter cake was washed once with cold water, filtered and dried to obtain methyl 3-amino-2-thiophenecarboxylate. The mass fraction was 97.8%, the yield was 84.7%, and the melting point was 60-63℃ [1]. Preparation of 2-Thiophenecarboxylicacid,3-fluoro-,methylester(9CI) methyl 3-amino-2-thiophenecarboxylate first reacts with NaNO₂ and HBr to generate diazonium bromide. Diazonium bromide then decomposes via a free radical mechanism under the catalysis of cuprous bromide to generate bromobenzene and nitrogen gas. The product is then subjected to halogen substitution with anhydrous KF to obtain 2-Thiophenecarboxylicacid,3-fluoro-,methylester(9CI).;
