Dimethylformamide → 3-(1-cyano-1-methylethyl)-N-(3-hydroxy-4-methoxyphenyl)benzamide

Participants

Reaction Steps

To a solution (20 mL) of 3-(1-cyano-1-methylethyl)benzoic acid (4.92 g, 26.0 mmol) in oxalyl chloride was added N,N-dimethylformamide (0.1 mL), and the mixture was stirred at room temperature for 30 min. Excess reagents were evaporated under reduced pressure, and the obtained residue was dissolved in tetrahydrofuran (20 mL), and 5-amino-2-methoxyphenol (4.17 g, 30.0 mmol) and N-ethyl-N-isopropylpropane-2-amine (6.46 g, 50.0 mmol) were successively added dropwise under ice-cooling. The reaction mixture was stirred at room temperature for 18 hr, poured into water and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in methanol (5 mL)/tetrahydrofuran (5 mL), 8N aqueous sodium hydroxide solution (1 mL) was added under ice-cooling, and the mixture was stirred at room temperature for 18 hr. The reaction mixture was poured into water and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (eluent:hexane/ethyl acetate=5:1), and triturated with diethyl ether to give the title compound (4.70 g, 58%) as a pale-yellow solid.

Provenance & Evidence