Potassium Iodide → Tert-butyl 3-(1-ethoxycarbonyl-3-cyclohexylpropyl)amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzoxazepine-5-acetate

Beteiligte Stoffe

Reaktionsschritte

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.

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