Hydrochloric Acid → 2'-Benzyloxy-4-carboxy-6'-hydroxychalcone

Participants

Reaction Conditions

Reaction Steps

To a mixture of 2′-benzyloxy-6′-hydroxyacetophenone (2.42 g) and methyl 4-formylbenzoate (2.46 g) in ethanol (50 mL) were added water (15 mL) and potassium hydroxide (6.73 g), and the mixture was stirred at 50° C. overnight. To the reaction mixture was added 2 mol/L hydrochloric acid (70 mL), and the precipitated crystals were collected by filtration. The crystals were washed with water and dried under reduced pressure to give 2′-benzyloxy-4-carboxy-6′-hydroxychalcone (3.55 g). This material was dissolved in N,N-dimethylformamide (35 mL). To the solution were added potassium carbonate (3.88 g) and methyl bromoacetate (1.95 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was dissolved in methanol (20 mL)-ethyl acetate (10 mL). To the solution was added 10% palladium-carbon powder (1 g), and the mixture was stirred at room temperature under a hydrogen atmosphere for 7 hours. The insoluble material was removed by filtration. The solvent of the filtrate was removed under reduced pressure, and the residue was treated with n-hexane. The precipitated crystals were collected by filtration and dried under reduced pressure to give 6′-hydroxy-2′-(methoxycarbonylmethoxy)-4-(methoxycarbonylme thoxycarbonyl)dihydrochalcone (2.56 g). This material was suspended in methanol (17 mL). To the suspension was added sodium methoxide (28% methanol solution, 3.35 mL), and the mixture was heated for ref lux overnight. The reaction mixture was cooled to room temperature. To the mixture was added 1 mol/L hydrochloric acid (30 mL), and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. To the residue were added methanol (25 mL) and 2 mol/L aqueous sodium hydroxide solution (50 mL), and the mixture was stirred at 60° C. overnight. The reaction mixture was cooled to room temperature. To the mixture were added 2 mol/L hydrochloric acid (55 mL) and water (50 mL), and the mixture was stirred at room temperature for 1 hour. The precipitated crystals were collected by filtration, washed with water and dried under reduced pressure to give 2-carboxy-3-[2-(4-carboxyphenyl)ethyl]-4-hydroxybenzofuran (1.45 g). This material was suspended in quinoline (12 mL). To the suspension was added a catalytic amount of copper powder, and the mixture was stirred at 200° C. for 1 hour. The reaction mixture was cooled to room temperature. To the mixture were added 1 mol/L hydrochloric acid and ethyl acetate, and the insoluble material was removed by filtration. The organic layer was separated from the filtrate. The organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent dichloromethane/methanol=20/1) to give the title compound (80 mg).

Provenance & Evidence