Hydrogen Bromide → Methyl 2-bromo-4-fluoro-5-methylbenzoate

Participants

Reaction Steps

To the suspension of methyl 2-amino-4-fluoro-5-methylbenzoate (2.2 g, 12 mmol) in 48% hydrobromic acid (80 mL) was added an aqueous solution (32 mL) of sodium nitrite (828 mg, 12 mmol) at 0° C., and the resulting solution was stirred for 30 min. Copper (I) bromide (1.72 g, 12 mmol) was added to the solution at 0° C. and the resulting reaction mixture was stirred at r.t for 1 h. After addition of ethyl acetate (200 mL), the reaction mixture was washed with water (200 mL×2), dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel eluted with PE-EA (10:1) to give methyl 2-bromo-4-fluoro-5-methylbenzoate (2.2 g, yield 74%) as colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.655 (d, J=8.0 Hz, 1H), 7.257 (d, J=8.5 Hz, 1H), 3.837 (s, 3H), 2.177 (s, 3H) ppm.

Provenance & Evidence