合成路线1

Chlorination of 1,4-benzodioxan (I) in AcOH afforded the 6,7-dichloro derivative (II). Subsequent Friedel-Crafts acylation of (II) with acetyl chloride and AlCl3 produced ketone (III), which was nitrated employing fuming nitric acid to give nitro compound (IV). Hydrogenation of the nitro group of (IV) with concomitant hydrogenolysis of the halogen atoms in the presence of Pd/C yielded amino ketone (V). After protection of the amino group of (V) as the corresponding acetamide (VI), chlorination by means of N-chlorosuccinimide provided (VII). Optionally, amide hydrolysis with NaOH afforded amine (VIII). Aldol condensation of (VIII) with pyridine-4-carboxaldehyde (IX) in ethanolic KOH gave rise to the unsaturated ketone (X). This compound was also obtained by condensation of the N-acetylated amino ketone (VII) with aldehyde (IX) in methanolic NaOH. In a related procedure, the aldol condensation of ketone (VIII) with aldehyde (IX) using LDA in cold THF produced hydroxy ketone (XI). This was further dehydrated to unsaturated ketone (X) by means of concentrated H2SO4. Hydrogenation of the olefinic double bond of (X) over Pd/C in THF generated the saturated ketone (XII). Further hydrogenation of the pyridine ring of (XII) using Rh/Al2O3 furnished the corresponding piperidine (XIII). Alternatively, (XIII) was obtained by direct hydrogenation of (X) over Rh/Al2O3.