Benzoic acid, 4-(acetyloxy)- → 2-(4-Hydroxyphenyl)-4-oxo-4h-chromene-6-carbonitrile

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Reaction Steps

2-Acetyl-4-cyanophenol (0.78 g, 4.84 mmol), 4-acetoxybenzoic acid (0.872 g, 4.84 mmol) and phosphorus oxychloride (0.5 mL) and pyridine (2.0 mL) were mixed in anhydrous dichloromethane (10 mL). The reaction mixture was stirred overnight at rt and then poured into cold water and extracted with dichloromethane (150 mL). The organic layer was washed with sodium bicarbonate, brine and dried over sodium sulfate followed by concentration. The crude compound (1.40 g, 89.5%) was obtained after evaporation of the solvent. The crude compound (1.4 g, 4.33 mmol) was dissolved into dry THF (20 mL) and potassium tert-butoxide (0.51 g, 4.55 mmol) was added and the reaction mixture was stirred at rt for 2 h. The solvent was removed, followed by addition of water (50 mL) and EtOAc (150 mL) was used to extract out the compound. The organic layer was washed with brine and dried over sodium sulfate. The crude product (1.20 g) and 4 drops of sulfuric acid were added to AcOH (15 mL). The reaction mixture was heated to 110° C. for 1 h. AcOH was removed and sodium bicarbonate solution was added followed by extraction with EtOAc. The organic layer was washed with brine and dried over sodium sulfate and concentrated. The crude and potassium carbonate (1.1 g) was added to MeOH (20 mL). The reaction mixture was stirred for 2 h. AcOH (1.0 mL) was added and MeOH was removed. The residue was purified by preparative HPLC to give 70 mg of 2-(4-hydroxyphenyl)-4-oxo-4H-chromene-6-carbonitrile. MS (ES) m/z: 264.91 (M+1), 263.90 (M); Mp. 296-298° C.

Provenance & Evidence