p-Toluenesulfonic acid → 4-{2-[1-(4-Chlorophenyl)ethylamino]ethyl}-1-(2-phenoxyethyl)piperidine

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Reaction Steps

In a similar manner to Example 31, a mixture of 4-(2-aminoethyl)piperidine (5.0 g), 4'-chloroacetophenone (6.04 g), p-toluenesulphonic acid (catalytic amount) and toluene (100 ml) was boiled under reflux for 10 hours with water removal using a Dean and Stark apparatus. The mixture was cooled to ambient temperature and 2-bromoethyl phenyl ether (7.85 g) and triethylamine (5.4 ml) added. The mixture was boiled under reflux for 6 hours. The solvent was evaporated off and the residue dissolved in ethanol (100 ml) and sodium borohydride (3.4 g) was added. The mixture was boiled under reflux for 4 hours then worked up to give an oil which was purified by flash column chromatography on silica using ethyl acetate/triethylamine (95:5) as the mobile phase to give 4-{2-[1-(4-chlorophenyl)ethylamino]ethyl}-1-(2-phenoxyethyl)piperidine as an oil.

Provenance & Evidence