合成路线1

The cyclization of 4-fluoro-alpha-methylstyrene (I) with ethylamine and refluxing aqueous formaldehyde gives (rac)-1-ethyl-3-(hydroxymethyl)-4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine (II), which is submitted to optical resolution by means of (-)-di-O-toluoyltartaric acid to yield (S)-isomer (III) and (R)-isomer (IV). The reduction of (S)-isomer (III) by means of LiAlH4 in THF yields (3S)-trans-1-ethyl-3-(hydroxymethyl)-4-(4-fluorophenyl)piperidine (V), which is condensed with 1,3-benzodioxol-5-ol (VI) by means of benzenesulfonyl chloride and TEA in dichloroethane to afford the aryl ether (VII). Finally, the ethyl group of (VII) is cleaved by means of 1-chloroethyl chloroformate and NaOH in toluene/water, followed by a treatment in refluxing methanol to provide the target paroxetine. The (R)-isomer (IV) can be profited by its reduction with H2 over Pd/C in methanol/AcOH/water to give (3R)-cis-1-ethyl-3-(hydroxymethyl)-4-(4-fluorophenyl)piperidine) (VIII), which is isomerized by means of NaOH in toluene/water and condensed with 1,3-benzodioxol-5-ol (VI) and NaOH in toluene/water to yield the already described aryl ether (VII).