Benzoate → Benzoic acid, 2-ethoxy-4-methyl-, ethyl ester

Participants

Reaction Steps

The ethyl 2-ethoxy-4-(2-<2-chloro-pyridine-3-carboxamido>ethyl)benzoate used as the starting material was prepared in the following manner: 2-hydroxy-4-methylbenzoic acid was reacted with K2CO3 and diethyl sulfate in acetone to give ethyl 2-ethoxy-4-methylbenzoate (boiling point at 1 mm=107°-108° C.), which was hydrolyzed to give the corresponding carboxylic acid (melting point 72°-74° C., from acetone). Subsequent bromination provided the 4-bromomethyl compound (melting point 98°-100° C.), which gave the 4-cyanomethyl compound (melting point 114°-117° C.) with sodium cyanide. Ethyl 2-ethoxy-4-(2-aminoethyl)benzoate hydrochloride was obtained by catalytic hydrogenation with Raney nickel and reaction with ethanolic hydrochloric acid, and this was reacted with 2-chloronicotinic acid, methyl chloroformate and triethylamine to give ethyl 2-ethoxy-4-(2-<2-chloro-pyridine-3-carboxamido>ethyl)benzoate (melting point 83°-85° C. after column purification).

Provenance & Evidence