合成路线1

A synthesis of [14C]-paroxetine labeled at the -CH2O- group has been described: 4-(4-Fluorophenyl)-1-methyl-1,2,5,6-tetrahydropyridine (I) is hydroxymethylated with [14C]-formaldehyde (II), yielding 4-(4-fluorophenyl)-1-methyl-1,2,5,6-tetrahydropyridine-3-methanol (III), which is hydrogenated with H2 over Pd/C in ethanol to give 4-(4-fluorophenyl)-1-methylpiperidine-3-methanol (IV) as a mixture of cis- and trans-isomers. The reaction of (IV) with phenylsulfonyl chloride and NaOH in water affords the corresponding sulfonate (V), which is then condensed with 3,4-(methylenedioxy)phenol (VI) by means of NaOH in toluene-4-methyl-2-pentanol, giving 4-(4-fluorophenyl)-1-methyl-3-[3,4-(methylenedioxy)phenoxymethyl]piperi dine (VII). The chromatographic separation of the trans-isomer of (VII), followed by its optical resolution with L-(+)-tartaric acid, affords optically pure (-)-(3S,4R)-N-methylparoxetine (VIII), which is finally demethylated with vinyl chloroformate and dry HCl.