The etherification of hydroquinone (I) with 2,2,2-trifluoroethyl trifluoromethanesulfonate (II) by means of K2CO3 in refluxing acetone gives the corresponding diether (III), which is submitted to a Friedel-Crafts condensation with Ac-Cl or Ac2O and AlCl3 in dichloromethane yielding the acetophenone (IV). The chlorination of (IV) with Cl2 in acetic acid at 55 C gives the alpha, alpha-dichloroacetophenone (V), which is further chlorinated with Cl2 and NaOAc in acetic acid at 100 C affording the corresponding trichloro derivative (VI). The reaction of (VI) with 2-(aminomethyl)pyridine (VII) in cyclohexane/toluene or isopropanol furnishes the benzamide (VIII), which is finally hydrogenated with H2 over Pt/C in isopropanol/acetic acid to give the target piperidine derivative.
The condensation of 2-aminomethylpyridine (II) with 2,2,2-trifluoroethyl-2,5-bis(2,2,2-trifluoroethoxy)benzoate (I) in refluxing glyme gives 2,5-bis(2,2,2-trifluoroethoxy)-N-(2-pyridylmethyl)benzamide (III), which is then hydrogenated with H2 over Pd/C in acetic acid.