Benzoyl Peroxide → Methyl 2-fluoro-5-formylbenzoate

Participants

Reaction Steps

Add N-bromosuccinimide (2.46 g, 13.86 mmol) and benzoyl peroxide (0.152 g, 0.630 mmol) to a solution of 2-fluoro-5-methyl-benzoic acid methyl ester (1.06 g, 6.30 mmol) in carbon tetrachloride (50 mL). Heat the mixture at reflux for 4 h. Cool the mixture to room temperature and wash with saturated aqueous sodium bicarbonate solution (10 mL) and brine (10 mL). Dry the organic layer over anhydrous sodium sulfate, filter, and concentrate under reduced pressure. Dissolve the resulting residue in dimethylsulfoxide (30 mL) and heat at reflux for 16 h. Cool the mixture to room temperature and dilute with water (100 mL) and ethyl acetate (100 mL). Extract the aqueous layer with ethyl acetate (3×100 mL). Wash the combined organic layers with water (3×100 mL), followed by brine (100 mL). Dry the organic layer over anhydrous sodium sulfate, filter and concentrate. Purify the residue by chromatography over silica gel, eluting with hexanes/ethyl acetate (80:20), to provide the title compound as a tan solid (0.228 g, 20%). 1H NMR (CDCl3, 300 MHz) δ 3.89 (s, 3H), 7.31-7.44 (m, 1H), 8.05-8.12 (m, 1H), 8.44-8.53 (m, 1H), 10.00 (s, 1H); TLC Rf=0.65 (3:1 Hexanes/Ethyl Acetate).

Provenance & Evidence