Synthesis of a novel cyclic sulfone dihydropyridine: An investigation of the isomerization reaction converting an exocyclic double bond isomer into a 1,4‐dihydropyridine

An eight membered cyclic sulfone 1,4‐dihydropyridine, RWJ 22726, 1, with remarkable cardiovascular activity was prepared by isomerization of an exocyclic double bond isomer using various reaction conditions. Under acidic and thermal isomerization conditions, an equilibrium mixture of products in an optimum ratio of 1:3.5 in favor of the desired 1,4‐dihydropyridine was obtained. Equilibration using basic reaction conditions could not be effected. Complete conversion to the 1,4‐dihydropyridine during the isomerization reaction was ultimately achieved by selective precipitation of the hydrochloride salt of the desired isomer.