2-Acetyl-4,5-dichlorothiophene

17249-79-5

68-12-2

57681-59-1

At -78 °C, n-butyllithium (2.51 g, 39.2 mmol, 24.5 mL) was slowly added dropwise to a stirred solution of diisopropylamine (3.97 g, 39.2 mmol, 5.54 mL) in tetrahydrofuran (5 mL) with continuous stirring for 45 min to generate lithium diisopropylamine (LDA) in situ. Subsequently, 2,3-dichlorothiophene (5 g, 32.7 mmol) dissolved in tetrahydrofuran (5 mL) was added dropwise and stirring was continued for 30 min at -78 °C. Next, N,N-dimethylformamide (3.41 g, 39.2 mmol, 3.64 mL) dissolved in tetrahydrofuran (5 mL) was added dropwise and the mixture was stirred at the same temperature for another 30 min. The cooling bath was removed and the reaction mixture was allowed to slowly warm up to room temperature. Upon completion of the reaction, the reaction was quenched with acetic acid/methanol (4 mL each) and stirred at room temperature for 15 minutes. The reaction mixture was diluted with ethyl acetate (50 mL) and washed sequentially with saturated aqueous sodium bicarbonate (25 mL), deionized water (25 mL) and saturated aqueous sodium chloride (25 mL). The organic layer was dried over anhydrous sodium sulfate (500 mg), and the desiccant was removed by filtration through crude glassine, followed by concentration under reduced pressure to give a white solid (9 g). The crude product was purified by fast column chromatography (eluent: EtOAc/hexane) to afford 2-acetyl-4,5-dichlorothiophene as a white powder (6.34 g, 19% yield). Mass spectrometry analysis showed a molecular ion peak (M + H)+ of 195.