5-CHLOROBENZOFURAN-2-CARBOXYLIC ACID

685-87-0

635-93-8

10242-10-1

General procedure for the synthesis of 5-chlorobenzofuran-2-carboxylic acid from diethyl bromomalonate and 5-chlorosalicylaldehyde: 5-chlorosalicylaldehyde (10.62 g, 67.8 mmol), diethyl bromomalonate (25.3 g, 105.8 mmol), and anhydrous potassium carbonate (9.37 g, 67.8 mmol) were suspended in ethylmethyl ketone (50 mL), and the reaction was carried out at reflux. The reaction was carried out for 5 h, followed by stirring at room temperature overnight. Upon completion of the reaction, the solvent was removed by evaporation and the residue was diluted with water (500 mL) and neutralized with 1N HCl solution. The resulting suspension was extracted with ether (Et2O) and the organic phase was dried over anhydrous magnesium sulfate (MgSO4) and concentrated. The oily residue was dissolved in anhydrous ethanol (50 mL) and 10% ethanol solution of potassium hydroxide (KOH) was added. The thick suspension formed was refluxed overnight under vigorous stirring. After cooling to room temperature, the solvent was removed by evaporation and water was added. The aqueous phase was washed with ether (Et2O) and the pH was subsequently adjusted to 2 with 1 N HCl. The aqueous suspension was extracted with ethyl acetate (EtOAc), and the organic phase was dried over anhydrous magnesium sulfate (MgSO4) and concentrated to give pure 5-chlorobenzofuran-2-carboxylic acid (7.4 g, 37.6 mmol, 55.5% yield) as a yellow oil.