1641-09-4

1108712-56-6

General procedure for the synthesis of 5-chloro-3-thiophenecarbonitrile from 3-cyanothiophene: Preparation of Intermediate 1M Synthesis: In a 100 mL three-necked round-bottomed flask, 3-cyanothiophene (5.0 g, 1 eq.) was dissolved in acetic acid (50 mL, 10 v/v), followed by N-chlorosuccinimide (6.73 g, 1.1 eq.). The reaction mixture was stirred at reflux temperature for 2-3 hours. The reaction progress was monitored by thin layer chromatography (TLC) using ethyl acetate: hexane (1:9) as mobile phase. Upon completion of the reaction, the mixture was cooled to room temperature and poured into an ice-water slurry (250 mL) and neutralized with sodium bicarbonate solution. The product was extracted with ethyl acetate (100 mL x 3). The organic layer was washed sequentially with brine solution (100 mL x 2) and dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure to give 5.0 g of crude product. Purification by fast column chromatography using ethyl acetate and hexane as eluents gave 2.4 g of pure product in 36.5% yield. MS/LCMS: m/z 177.0. nuclear magnetic resonance spectroscopy (NMR) confirmed the structure.