SYNTHESIS OF -[1-(3-BENZOYL-4-PHENYL-1,4-DIHYDROPYRIDYL)]ACETIC ACID METHYL-ESTER, ACETIC-ACID, AND ACETAMIDE ANALOGS AS POTENTIAL ANTIARTHRITIC AGENTS

The cuprous iodide catalyzed reaction of -methyl-2-[1-(3-benzoyl-4-phe nylpyridinium)]acetic acid methyl ester bromide (5), prepared by react ion of 3-benzoylpyridine (4) with racemic methyl 2-bromopropionate, wi th phenylmagnesium chloride at -23 degrees C afforded the 2-[1-(3-benz oyl-4-phenyl-1,4-dihydropyridyl)acetic acid methyl ester (6, 74%), whi ch was a mixture of four diastereomers. Recrystallization of this dias tereomeric mixture from diethyl ether afforded a solid product (6a-sol id, 30%, 4R, 2R* and 4S*, 2S*) and an oil product (6b-oil, 39%, 4R*, 2S and 4S*, 2R*), each consisting of a mixture of two diastereomers t hat differ in relative configuration (R or S*) at the 1,4-dihydropyri dine C-4 position and the -CH(Me)CO2Me moiety. Addition of the Grignar d reagent from either of the two diastereotopically different faces of the planar pyridinium salt (5) gives rise to two diastereomeric produ cts 6a-solid and 6b-oil in which the C-4 phenyl substituent is pseudoa xial to the boat-shaped 1,4-dihydropyridine ring. Alkaline hydrolysis, or ammonolysis, of the acetic acid methyl ester (6) afforded the resp ective acetic acid (7), or acetamide (8), derivative.