Acetone → Methyl 3-fluoro-2-methoxybenzoate

Participants

Reaction Steps

A mixture containing 3-fluorosalicylic acid (20 g) [obtained as white crystals, m.p. 145°-147° C., by the method of L. N. Ferguson et alia, J.Amer.Chem.Soc., 1950, 72, 5315], iodomethane (60 g), potassium carbonate (40 g) and acetone (200 ml) was heated under reflux for 24 hours. Water (500 ml) was added and the mixture was extracted with ether (3×150 ml). The combined extracts were dried (MgSO4) and evaporated to give methyl 3-fluoro-2-methoxybenzoate (B) (21 g) as a yellow oil, which was used without further purification; NMR: 3.85 (3H,s), 3.95 (3H,s) and 6.8-7.6 (3H,m). (ii) A solution containing B (15.9 g), potassium hydroxide (25 g) and water (5 ml) in methanol (200 ml) was stirred for 4 hours. The solvent was evaporated and the residue was dissolved in water (200 ml). The aqueous solution was washed with ether (100 ml) and acidified to pH2 with concentrated hydrochloric acid. The white precipitate was collected by filtration and recrystallised from hexane to give 3-fluoro-2-methoxybenzoic acid (C) (14.2 g) as white crystals. [Further material (6.1 g) was obtained by extraction of the filtrate with ethyl acetate (100 ml).]

Provenance & Evidence