Condensation of isonicotinamide (I) with 1-chloro-2,4-dinitrobenzene (II) gave quaternary pyridinium salt (III). This was further converted into pyridinium salt (V) by treatment with 2-methoxyaniline (IV) in MeOH. Catalytic transfer hydrogenation of the pyridine ring of (V) provided piperidine (VI). The amide function of (VI) was then reduced to amine (VII) using either borane-dimethyl sulfide complex or LiAlH4. Condensation of 4-chlorocatechol (VIII) with epichlorohydrin (IX) in aqueous KOH produced a mixture of regioisomeric benzodioxans (X) and (XI), from which the major 7-chloro isomer (X) was isolated by flash chromatography after treatment with tosyl chloride and pyridine yielding tosylate (XII). This compound was finally coupled with amine (VII) in the presence of K2CO3 and KI in boiling acetonitrile.

The reaction of 5-chloro-2-hydroxybenzaldehyde (I) with the chiral glycidyl tosylate (II) by means of K2CO3 in DMF gives the condensation product (III), which is oxidized with m-chloroperbenzoic acid to formyl ester (IV). The cyclization of (IV) with sodium methoxide in methanol affords the hydroxymethyl benzodioxane (V), which is tosylated with tosyl chloride in pyridine to the tosylate (VI). Finally, this compound is condensed with 1-(2-methoxyphenyl)piperidin-4-ylmethylamine (VII) by means of K2CO3 in refluxing acetonitrile.