Methyl iodide → 1-(4-Bromo-2-fluorophenyl)ethan-1-one

Participants

Reaction Steps

Into a 500-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of Mg (6 g, 250.00 mmol, 2.60 equiv) in diethyl ether (50 mL). To the resulting mixture was then added a solution of CH3I (118.4 g, 833.80 mmol, 7.80 equiv) in diethyl ether (75 mL) dropwise with stirring at room temperature. The resulting solution was allowed to react for 1 hr at room temperature. The above methylmagnesium iodide solution (2M) was then added to a solution of 4-bromo-2-fluoro-N-methoxy-N-methylbenzamide (25 g, 95.42 mmol, 1.00 equiv) in tetrahydrofuran (150 mL) dropwise with stirring at −20° C. The resulting solution was stirred for an additional 2 h at room temperature. The resulting mixture was cooled to 0° C. with a water/ice bath. The reaction was then quenched by the addition of NH4Cl/H2O (300 mL). The resulting solution was extracted with ethyl acetate (2×200 ml) and the organic layers combined. The resulting mixture was washed with water (1×200 mL) and brine (1×200 mL). The resulting mixture was dried over NaSO4 and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate:PE (1:20) to yield 1-(4-bromo-2-fluorophenyl)ethanone as colorless oil.

Provenance & Evidence