反应详情

温度

0 °C

To a stirred solution of 3-(10,11 -dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propanol (1.17 g, 0.0046 mol, prepared similarly as described in example 2) and triethylamine (1.18 g, 0.012 mol) in toluene (30 ml) at 0° C., methanesulfonyl chloride (0.70 ml, 0.009 mol) was added dropwise over 10 minutes. The resulting mixture was stirred at 0° C. for 1 h. Toluene (50 ml) and water (100 ml) were added, and the phases were separated. The aqueous layer was extracted with toluene (50 ml), and the combined organic phases were washed with brine (2×100 ml), dried (MgSO4) and concentrated in vacuo. The residue was dissolved in acetonitrile (10 ml) and the above 2-piperazine-carboxylic acid ethyl ester (1.40 g, 0.0089 mol), potassium carbonate (0.67 g, 0.0049 mol) and toluene (5 ml) were added. The resulting mixture was heated at reflux temperature for 18 h. Water (50 ml) was added, and the mixture was extracted with ethyl acetate (3×20 ml). The combined organic extracts were washed with brine (2×20 ml), dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel (27 g) using a gradient of methanol and ethyl acetate (5:100→20:100), affording 0.6 g (33%) of 4-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propyl)-2-piperazinecarboxylic acid ethyl ester as an oil.

1. customat 0° C.
2. customthe phases were separated
3. extractionThe aqueous layer was extracted with toluene (50 ml)
4. washthe combined organic phases were washed with brine (2×100 ml)
5. dry with materialdried (MgSO4)
6. concentrationconcentrated in vacuo
7. dissolutionThe residue was dissolved in acetonitrile (10 ml)
8. temperatureThe resulting mixture was heated
9. temperatureat reflux temperature for 18 h
10. extractionthe mixture was extracted with ethyl acetate (3×20 ml)
11. washThe combined organic extracts were washed with brine (2×20 ml)
12. dry with materialdried (MgSO4)
13. concentrationconcentrated in vacuo
14. customThe residue was purified by column chromatography on silica gel (27 g)