1-(2-fluoro-3-nitrophenyl)ethanone

58534-94-4

97674-02-7

873697-78-0

General procedure for the synthesis of 1-(2-fluoro-3-nitrophenyl)ethanone from 2-fluoro-3-bromonitrobenzene and tributyl(1-ethoxyvinyl)tin: Dichlorobis(triphenylphosphine)palladium(II) (1.6 g, 2.28 mmol, 0.05 eq.) was added to a dioxane solution of 2-fluoro-3-bromonitrobenzene (100 mL, 10.0 g, 45.6 mmol, 1 eq.). 1equivalent), the resulting turbid solution was heated at 90 °C for 4 h. The solution gradually changed to dark brown during the reaction. The progress of the reaction was monitored by thin layer chromatography (TLC, unfolding agent 30% methyl tert-butyl ether/heptane) and after confirming the complete conversion of the feedstock, the reaction mixture was cooled to room temperature. A saturated solution of potassium fluoride (KF, 100 mL) and ethyl acetate (100 mL) was added to the reaction mixture and the two-phase mixture was stirred for 1 h. The mixture was subsequently filtered through diatomaceous earth and washed with ether. The organic layer was separated, dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to give the crude product as a brown oil in the form of an enol ether. The crude product was dissolved in tetrahydrofuran (THF, 50 mL), 2N hydrochloric acid (50 mL) was added and the reaction mixture was stirred at room temperature. After completion of the reaction, the reaction mixture was saturated with sodium chloride (NaCl) and extracted with methyl tert-butyl ether (MTBE, 2 x 150 mL). The organic layers were combined, washed once with brine (30 mL), dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography with an eluent of 0-40% ethyl acetate/heptane gradient solution. The fraction containing the target product was collected and the solvent was evaporated under reduced pressure to give 1-(2-fluoro-3-nitrophenyl)ethanone as a yellow oil (7.1 g, 86% yield).