1-(4-chloro-2-nitrophenyl)ethanone

41995-04-4

105-53-3

23082-51-1

Sodium hydride (NaH, 3.6 g, 90 mmol) was added to a tetrahydrofuran (THF, 250 mL) solution of diethyl malonate (12.0 g, 75 mmol) in batches and the reaction mixture was stirred for 20 min at room temperature. Subsequently, a tetrahydrofuran (THF, 100 mL) solution of 4-chloro-2-nitrobenzoyl chloride was slowly added dropwise into the reaction system at 0 °C. After the dropwise addition, stirring was continued for 30 min at room temperature, and then the reaction was warmed up to 80 °C for 2 h. The reaction was carried out at 0 °C for 2 h. The reaction was carried out at 0 °C for 2 h. Upon completion of the reaction, the reaction was quenched with water and extracted with ethyl acetate and water by partitioning. The organic phase was collected, dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure. The concentrated residue was dissolved in a mixed solution of acetic acid (AcOH, 25 mL) and 20% sulfuric acid (H2SO4, 25 mL), and the reaction was stirred at 80 °C for 6 hours. At the end of the reaction, the reaction mixture was extracted with ethyl acetate and the organic phase was washed sequentially with saturated saline, water and sodium bicarbonate (NaHCO3) solution. The organic phase was dried again with anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure. Finally, the residue was purified by silica gel fast column chromatography (eluent: ethyl acetate/petroleum ether=1:5) to afford the target product 1-(4-chloro-2-nitrophenyl)ethanone (5.0 g, 33% yield) as a light yellow solid.