A mixture of sodium hydride (0.40 g, 0.010 mol, 60% oil dispersion) and 10,11-dihydro-5H-dibenz[b,f]azepine (1.95 g, 0.010 mol) in dry dibutylether (30 ml) was heated at reflux temperature for 3.5 h under an atmosphere of nitrogen. The reaction mixture was cooled to 100° C. and bis-2-chloro-ethyl ether (4.7 ml) was added and the mixture was heated at reflux temperature for 16 h. The reaction mixture was cooled and water (50 ml) was added. The mixture was extracted with toluene (100 ml). The organic extract was dried over sodium sulphate and the solvent evaporated in vacuo to give 2.8 g of an oily residue containing 2-chloro-1-(2-(10,11-dihydro-5H-dibenz[b,f]-azepin-5-yl)ethoxy)ethane. To this oil was added ethyl (R)-3-piperidinecarboxylate (3.0 g, 0.019 mol) and the mixture was heated at 150° C. for 1.5 h. The reaction mixture was allowed to cool to 80° C. and toluene (100 ml) was added. The mixture was then allowed to cool to room temperature and a solution of potassium carbonate (1.4 g) in water (100 ml) was added. The phases were separated and the organic phase was washed successively with water, an aqueous sodium acetate solution (pH 5) and an aqueous citric acid solution (pH 5). The organic phase was then extracted with a 5% aqueous citric acid solution (50 ml). The acidic (pH 1) aqueous extract was washed with toluene (2×50 ml) and then a 4 N sodium hydroxide solution was added until pH 6-7. The aqueous mixture was extracted with toluene and the organic extract was treated with charcoal and dried over sodium sulphate. The solvent was evaporated in vacuo to give 2.1 g (50%) of (R)-N-(2-(2-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)ethoxy)ethyl)-3-piperidinecarboxylic acid ethyl ester as an oil. TLC: rf=0.20 (SiO2 ; n-heptane/THF=7:3).
