3-Nitrobenzaldehyde → 3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-, 3-(2-cyanoethyl) 5-methyl ester

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The compounds of the invention can be prepared by esterification of the enantiomers of methyl 3-carboxy-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-5-pyridinedicarboxylate with the enantiomers of 1-azabicyclo[2.2.2]octan-3-ol (3-quinuclidinol). The acid may be prepared by condensation of 3-nitrobenzaldehyde with methyl 3-aminocrotonate and 2-cyanoethyl acetoacetate to afford 2-cyanoethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate which may be hydrolyzed with one equivalent of a suitable base (G.B. Patent 2122192), e.g. NaOH, to give methyl 3-carboxy-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-5-pyridinedicarboxylate. Resolution of the acid is achieved by recrystallization of the cinchonidine (U.S. Pat. No. 4,920,225) addition salt from ethanol free chloroform. The enantiomers of 3-quinuclidinol are obtained by the procedure of B. Ringdahl, B. Resul and R. Dahlbom (Acta. Pharm. Seuc., 1979, 16, 281).

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