3-Amino-p-cresol → 3-(1-cyanocyclopropyl)-N-(5-hydroxy-2-methylphenyl)benzamide

Participants

Reaction Steps

To a two-layer solution of 3-amino-4-methylphenol (5.92 g, 48.0 mmol) in tetrahydrofuran (40 mL )/1N aqueous sodium hydrogen carbonate solution (54 mL) was added a solution of 3-(1-cyanocyclopropyl)benzoyl chloride synthesized above in tetrahydrofuran (20 mL), and the mixture was stirred at room temperature for 2 hr. Since the pH of the reaction mixture was 4-5, sodium hydrogen carbonate (900 mg, 10.7 mmol) was added to the mixture to adjust the pH to 8-9, and the reaction mixture was further stirred at room temperature for 1 hr. The aqueous layer was separated, and extracted with ethyl acetate (150 mL). The combined organic layer was washed with saturated brine (150 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. Ethyl acetate (25 mL)/hexane (50 mL) was added to the obtained suspension, and the mixture was stirred at room temperature for 20 min. The precipitate was collected by filtration, washed repeatedly with diisopropyl ether/hexane (1:1), and air-dried to give the title compound (12.2 g, 87%) as a pale-yellow powder.

Provenance & Evidence