Methyl iodide → 1-Bromo-2,4-difluoro-5-methoxybenzene

Participants

Reaction Conditions

Reaction Steps

To a solution of 1,3 dibromo-4,6-difluorobenzene (10.0 g, 37 mmol) in THF (50 mL) at −20° C. was added isopropyl magnesium chloride (2.0M in THF, 42 mmol) and the resulting solution warm to 0° C. and stirred for 30 minutes. Trimethylborate (4.7 g, 45 mmol) was added and the mixture stirred at ambient temperature for 1 hour. The solution was recooled to −20° C. and peracetic acid (32%, 50 mmol) was added and the solution was stirred for 30 minutes at ambient temperature. The solution was then quenched with sodium bisulfite (5% solution, 75 mL) and then acidified with 6 N hydrochloric acid and extracted with ethyl ether (2×75 mL). Combined extracts were dried (sodium sulfate) and concentrated. The crude phenol was dissolved in acetonitrile (40 mL) and potassium carbonate (10 g, 74 mmol) and iodomethane (5.7 g, 40 mmol) were added and stirred at ambient temperature for 20 hours. The solution was concentrated and the residue taken into water (50 mL) and extracted with ethyl ether (2×75 mL) and the combined extracts were washed with brine, dried (sodium sulfate), and concentrated. The residue was purified by chromatography (hexanes) to give 1-bromo-2,4-difluoro-5-methoxybenzene (2.0 g, 8.6 mmol): LC/MS (m/z=223).

Provenance & Evidence