Ethyl 4-piperidinecarboxylate → 1-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2-hydroxy-propyl)-4-piperidinecarboxylic acid ethyl ester

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Reaction Steps

A mixture of crude (10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2,3-epoxypropane (22.6 g, 90 mmol, prepared as described in Example 19) and 4-piperidinecarboxylic acid ethyl ester (14.15 g, 90 mmol) in dry 2-butanone (50 ml) was stirred and heated at reflux temperature for 24 h. The solvent was removed in vacuo and the residue was dissolved in toluene (250 ml) and water (250 ml). The pH was adjusted to 6 by addition of 1 N hydrochloric acid. The organic phase was separated, washed with water (3×100 ml), dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a mixture of toluene, ethyl acetate and triethylamine (20:20:1) as eluent to give 5.8 g (16%) of 1-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-2-hydroxy-propyl)-4-piperidinecarboxylic acid ethyl ester as an oil.

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