An Isoxazole Strategy for the Synthesis of Fully Substituted Nicotinates

A four-step quasi one-pot procedure for the preparation of fully substituted nicotinates from ketone enamines and 4-methylideneisoxazol-5-ones has been developed. The reaction sequence involves (1) reaction of 4-methylideneisoxazol-5-ones with ketone enamines with the formation of isoxazole-5-ols, (2) their O-methylation with diazomethane, (3) hydrogenative cleavage of the O–N bond in 5-methoxyisoxazoles under action of Mo(CO)6/H2O and simultaneous isomerization and condensation of the formed enamines, with the formation of dihydropyridines, and (4) aromatization of the latter.