5-Amino-2-methylphenol → 3-(1-cyano-1-methylethyl)-N-(3-hydroxy-4-methylphenyl)benzamide

Participants

Reaction Steps

To a solution of 3-(1-cyano-1-methylethyl)benzoic acid (5.00 g, 26.4 mmol) in tetrahydrofuran (50 mL) were added N,N-dimethylformamide (40 μL) and oxalyl chloride (3.20 mL, 36.5 mmol), and the mixture was stirred at room temperature for 1.5 hr. The reaction mixture was concentrated under reduced pressure to give 3-(1-cyano-1-methylethyl)benzoyl chloride. To a solution of 5-amino-2-methylphenol (3.00 g, 24.3 mmol) in tetrahydrofuran (20 mL) was added an aqueous suspension (30 mL) of sodium hydrogen carbonate (3.00 g, 36.5 mmol), and the mixture was vigorously stirred at room temperature. To this mixture was added dropwise under ice-cooling a solution of the above-mentioned 3-(1-cyano-1-methylethyl)benzoyl chloride in tetrahydrofuran (30 mL), and the mixture was stirred at room temperature for 5 hr. The aqueous layer of the reaction mixture was separated, and the organic layer was diluted with ethyl acetate (200 mL) and washed with saturated brine (200 mL). The extract was dried over anhydrous magnesium sulfate and decolored with activated carbon. The insoluble material was filtered off through a pad packed with silica gel and celite in two layers. The solvent was evaporated under reduced pressure, and the obtained solid was washed with a mixed solvent of ethyl acetate and hexane to give the title compound (6.75 g, 94%) as a white powder.

Provenance & Evidence