反应详情

温度

-75 °C

To a solution of 5.0 g (18 mmol) (S)-(2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl)-carbamic acid tert-butyl ester in 80 ml of tetrahydrofuran at −75° C. 18 ml (18 mmol) of lithium bis(trimethylsilyl)amide solution (1M in tetrahydrofurane) was added. After stirring for 30 min at −75° C. the mixture was allowed to reach room temperature and 3.07 g (21.6 mmol) of methyl iodide was added. The mixture was stirred for 2.5 hours at room temperature and concentrated in vacuo. The residue was distributed between 1M NaHSO4 solution and ethyl acetate. The combined organic layers were reextracted with water and dried (MgSO4). After evaporation of the solvent 20 ml of dichlorometane and 20 ml of trifluoracetic acid was added and the mixture was stirred for 2.5 h at room temperature. For workup the mixture was concentrated in vacuo, then ethylacetate was added and the mixture was extracted two times with water. The aqueouos phase was basified with sodium hydroxide and extracted three times with ethyl acetate. The combined organic layers were dried (MgSO4) and evaporated. The residue was purified by column chromatography (dichloromethane/methanol=9:1) to yield 2.1 g (65%) of (S)-3-amino-1-methyl-1,3,4,5-tetrahydro-benzo[b][1,4] diazepin-2-one.

1. customat −75° C
2. customto reach room temperature
3. stirringThe mixture was stirred for 2.5 hours at room temperature
4. concentrationconcentrated in vacuo
5. dry with materialdried (MgSO4)
6. customAfter evaporation of the solvent 20 ml of dichlorometane and 20 ml of trifluoracetic acid
7. additionwas added
8. stirringthe mixture was stirred for 2.5 h at room temperature
9. concentrationFor workup the mixture was concentrated in vacuo
10. additionethylacetate was added
11. extractionthe mixture was extracted two times with water
12. extractionextracted three times with ethyl acetate
13. dry with materialThe combined organic layers were dried (MgSO4)
14. customevaporated
15. customThe residue was purified by column chromatography (dichloromethane/methanol=9:1)