反应详情

A mixture of 3(S)-amino-2,3,4,5-tetrahydro-1,5-benzoxazepine-4-one hydrochloride (2 g), ethanol (100 ml), sodium acetate (0.8 g), acetic acid (0.6 g), molecular sieves 4A (5 g) and ethyl 4-cyclohexyl-2-oxo-butyrate (5 g) is catalytically hydrogenated over Raney nickel at room temperature under atmospheric pressure. After the absorption of hydrogen ceases, the catalyst is removed by filtration and the filtrate is evaporated in vacuo. To the residue are added water (50 ml) and ethyl acetate (200 ml), and the mixture is agitated thoroughly. The ethyl acetate layer is dried over anhydrous magnesium sulfate and evaporated in vacuo to yield an oily residue containing 3-(1-ethoxycarbonyl-3-cyclohexylpropyl)amino-2,3,4,5-tetrahydro-1,5-benzoxazepine-4-one. A mixture of this oil, potassium carbonate (4 g), tert-butyl chloroacetate (3 g), potassium iodide (0.2 g) and N,N-dimethylformamide (20 ml) is stirred overnight at room temperature, and then diluted with a mixture of water (300 ml) and ethyl acetate (200 ml). The organic layer is separated, dried over anhydrous magnesium sulfate and evaporated in vacuo to yield an oil, which is purified by silica gel column chromatography using hexaneethyl acetate (4:1) as an eluant to yield tert-butyl 3-(1-ethoxycarbonyl-3-cyclohexylpropyl)amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate (1 g) as a colorless oil.

1. customAfter the absorption of hydrogen ceases
2. customthe catalyst is removed by filtration
3. customthe filtrate is evaporated in vacuo
4. additionTo the residue are added water (50 ml) and ethyl acetate (200 ml)
5. dry with materialThe ethyl acetate layer is dried over anhydrous magnesium sulfate
6. customevaporated in vacuo
7. customto yield an oily residue
8. stirringis stirred overnight at room temperature
9. customThe organic layer is separated
10. dry with materialdried over anhydrous magnesium sulfate
11. customevaporated in vacuo
12. customto yield an oil, which
13. customis purified by silica gel column chromatography