反应详情

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.

1. temperatureheated
2. temperatureat reflux temperature for 24 h
3. customThe solvent was removed in vacuo
4. dissolutionthe residue was dissolved in toluene (250 ml)
5. additionThe pH was adjusted to 6 by addition of 1 N hydrochloric acid
6. customThe organic phase was separated
7. washwashed with water (3×100 ml)
8. dry with materialdried (MgSO4)
9. concentrationconcentrated in vacuo
10. customThe crude product was purified by column chromatography on silica gel using
11. additiona mixture of toluene, ethyl acetate and triethylamine (20:20:1) as eluent