4-Chlorobenzylamine → HCID 178510744, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of 4-aminobenyl cyanide (6.61 g) and diethyl ethoxymethylene-malonate (10.1 mL) is heated to 95° C. for 1 hour. The reaction is cooled to room temperature and poured into 50 mL hexanes to wash away impurities. The desired enamine intermediate formed upon cooling and is filtered and collected. In a 3-necked roundbottom connected to a Dean-Stark trap, 75 mL of diphenyl ether is added to the enamine and the solution is heated at 250° C. for 2 hours. The crude product is washed with hot MeOH and dried to yield 3.40 g of ethyl 6-cyanomethyl-4-hydroxyquinoline-3-carboxylate as an orange solid. A mixture of this ester (0.50 g) and p-chlorobenzylamine (3.5 mL) are heated at 180° C. for 1 hour. The reaction is cooled to room temperature and diluted with CH2Cl2 and ether. The solvents are evaporated. The residue is chromatographed on silica, eluting with 3% MeOH in CH2Cl2. Fractions homogenous by TLC are combined, condensed and recrystallized with EtOAc/hexanes to yield 0.162 g of the desired product as a light yellow solid.

Provenance & Evidence