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RS-25259-197 can be obtained by several related ways: 1) The condensation of naphthalene-1,8-dicarboxylic anhydride (I) or the corresponding imide (II) with quinuclidin-3(S)-amine (III) in refluxing isopropanol gives 2-[3(S)-quinuclidinyl]-2,3-dihydro-1H-benz[de]isoquinoline-1,3-dione (IV), which by hydrogenation with H2 over PtO2 in ethanol yields 3-hydroxy-2-[3(S)-quinuclidinyl]-2,3,3a,4,5,6-hexahydro-1H-benz[de]isoquionlin-1-one (V). The dehydration of (V) with HCl in refluxing isopropanol affords the 2,4,5,6-tetrahydro compound (VI) (1), which is finally hydrogenated with H2 over Pd/C in acetic acid to yield a mixture of (S,S)- and (R,S)-diastereomers that is resolved by crystallization and chromatography. 2) The partial hydrogenation of anhydride (I) with H2 over Pd/C in hot acetic acid gives 3-acetoxy-5,6-dihydro-1H,4H-naphtho[1,8-cd]pyran-1-one (VIII), which is deacetylated by hydrogenation with H2 over Pd/C in ethyl acetate, yielding 5,6-dihydro-1H,4H-naphtho[1,8-cd]pyran-1-one (IX). Finally, this compound is condensed with the quinuclidine (III) by heating at 140 C and digestion with methanol to afford the hydroxy compound (V), already obtained. 3) The cyclization of N-[3(S)-quinuclidinyl]-5,6,7,8-tetrahydronaphthalene-2-carboxamide (X) by means of butyllithium and DMF gives the 2,4,5,6-tetrahydro compound (VI), already obtained.

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