Sodium Hydroxide → 5-Fluoro-2-methoxybenzoic acid

Participants

Reaction Steps

To a solution of 5-fluoro-2-methoxybenzaldehyde (1 g) in acetone (4 mL) was added a solution of potassium permanganate (1.54 g) in water (16 mL), and the mixture was heated for reflux for 4 hours. The reaction mixture was cooled to room temperature. To the mixture was added 2 mol/L aqueous sodium hydroxide solution (5.2 mL), and the insoluble material was removed by filtration. The filtrate was washed with ethyl acetate. The aqueous layer was acidified by addition of 2 mol/L hydrochloric acid, and the mixture was extracted with ethyl acetate twice. The extracts were combined and washed with brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/1−ethyl acetate) to give 5-fluoro-2-methoxybenzoic acid (0.66 g). This material was dissolved in N,N-dimethylformamide (15 mL). To the solution were added potassium carbonate (0.63 g) and iodomethane (0.26 mL), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate, and the resulting mixture was washed with water and brine successively, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give methyl 5-fluoro-2-methoxybenzoate (0.7 g). This material was dissolved in tetrahydrofuran (10 mL). To the solution was added methylmagnesium iodide (3.0 mol/L diethyl ether solution, 3.82 mL) under ice-cooling, and the mixture was stirred at room temperature for 2 hours. To the reaction mixture was added a saturated aqueous ammonium chloride solution, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine successively, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane−n-hexane/ethyl acetate=1/1) to give the title compound (0.65 g).

Provenance & Evidence