Hydrochloric Acid → 5-Fluoro-2,4-dimethoxybenzoic acid

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Reaction Conditions

Reaction Steps

A solution of 3.1 g (17.2 mmol) of 2,4-dimethoxy-5-fluorobenzonitrile and 100 mL of 6N aqueous sodium hydroxide in 200 mL of methanol was stirred at reflux overnight, cooled to 0° C., acidified to pH 1-2 with 6N aqueous hydrochloric acid, and partitioned between ethyl acetate and brine. The organic extract was dried over Na2SO4, and the solvents were removed in vacuo to give crude 2,4-dimethoxy-5-fluorobenzoic acid as a light-yellow solid. Recrystallization from ethyl acetate and hexane afforded 3.2 g (93%) of 6 as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 12.4 (s, 1H), 7.49 (d, 1H, J=12 Hz), 6.83 (d, 1H, J=7.2 Hz), 3.92 (s, 3H), 3.84 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 165.5, 165.5, 156.7, 151.1, 151.0, 146.3, 143.2, 117.9, 117.6, 111.2, 111.1, 99.3, 56.6, 56.4; 19F NMR (282 MHz, DMSO-d6) δ −146.2 (dd, 1F); mass spectrum, calculated for C9H9FO4 (MH+) 201.1, Found 200.9.

Provenance & Evidence