Potassium Carbonate → Ethyl 4-hydroxy-2-methylbenzofuran-6-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of ethyl 4-acetoxy-2-methylbenzofuran-6-carboxylate (I-1b: 549.03 g, 1.37 mol) in ethanol (4.00 L) at room temperature was added potassium carbonate (266 g, 1.92 mol) in one portion. The reaction mixture was then heated at 60° C. for 3 hours. Potassium carbonate (100 g, 0.720 mol) was then added in one portion and the reaction mixture was heated at 60° C. for a further 3 hours. After cooling to room temperature the mixture was diluted with dichloromethane (2 L) and the suspension filtered, washing the solids with dichloromethane (2×1 L) (all batches were combined at this point). The combined filtrate and washings were then washed with citric acid (2.5 L of a 1 M aqueous solution), then concentrated in vacuo and the resulting residue purified by dry flash chromatography (hexane then 2:1 hexane:ethyl acetate). All fractions containing the desired product were combined and concentrated in vacuo. The resulting residue, which solidified on standing, was slurried with cold toluene and filtered. The solids were then stirred with hot toluene and decolourising charcoal for 1 hour, followed by filtration of the hot mixture through a pad of celite. The filtrate was allowed to cool and the resulting precipitate isolated by filtration to give desired ethyl 4-hydroxy-2-methylbenzofuran-6-carboxylate (I-1c: 360 g, 90%) as orange powder. 1H NMR (CDCl3, 300 MHz) δ ppm 7.73-7.73 (m, 1H), 7.45 (d, 1H), 6.51-6.50 (m, 1H), 5.85 (s, 1H), 4.39 (q, 2H), 2.48 (d, 3H), 1.40 (t, 3H). LCMS (liquid chromatography mass spectrometry): m/z 221.06 (96.39% purity).

Provenance & Evidence