2-Aminophenol → HCID 178469673, compound

Participants

Reaction Steps

A mixture of 2-aminophenol (5.457 g) and diethyl ethoxymethylenemalonate (10.81 g) is heated to 130° C. for 2 h with removal of ethanol by a Dean-Stark trap. The reaction is cooled to room temperature. Diphenyl ether (50 mL) is added and the mixture is heated to 240° C. for 90 min with removal of ethanol by a Dean-Stark trap. The solution is cooled to room temperature and the resulting solid is collected and washed with hexanes. The crude solid is recrystallized from acetone to yield 0.650 g of ethyl 4,8-dihydroxyquinoline-3-carboxylate. A mixture of this ester (0.500 g) and 4-chlorobenzylamine (1.518 g) are heated to 180° C. for 1 h. The solution is cooled to room temperature and diluted with CH2Cl2. The resulting solid is collected and chromatographed on silica, eluting with 3% MeOH/CH2Cl2. Fractions homogeneous by TLC are combined and concentrated in vacuo. The residue is sonicated with CH2Cl2 /hexanes. The resulting solid is collected and dried to afford 0.349 g of the desired product as an off-white solid.

Provenance & Evidence