反应详情

[4-(1-Ethoxymethyl-1H-imidazol-2-yl)-1-isopropyl-3-methyl-4-oxo-but-2-enyl]-methyl-carbamic acid tert-butyl ester (496 mg, 1.31 mmole) is stirred in 4N hydrochloric acid/dioxane at room temperature under nitrogen for 2 hours. The solvent is removed in vacuo. Dichloromethane is added to the residue and evaporated (this step is repeated twice) to give a white solid amino intermediate which then stirred with 2-tert-Butoxycarbonylamino-3,3-dimethyl-butyric acid (410.5 mg, 1.78 mmole), 3-(diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one (DEPBT, 531 mg, 1.77 mmole) and triethylamine (0.49 ml, 3.55 mmole) in 4 ml dichloromethane at room temperature overnight. The reaction mixture is diluted with dichloromethane/water. Organic layer is separated. The aqueous layer is extracted twice with dichloromethane. The combined organic extracted are washed with citric acid (4 ml), sodium carbonate (6 ml) and brine, dried over sodium sulfate, filtered, concentrated in vacuo. The residue is flash chromatographed with hexane/ethyl acetate from 5:1 to 1:1 to give a white crystals, (1-{[4-(-Ethoxymethyl-1H-imidazol-2-yl)-1-isopropyl-3-methyl-4-oxo-but-2-enyl]-methyl-carbonyl}-2,2-dimethyl-propyl)-carbamic acid tert-butyl ester: 171 mg (26%). MS(ES+): (M+H)=493.2

1. customThe solvent is removed in vacuo
2. additionDichloromethane is added to the residue
3. customevaporated (this step
4. customto give a white solid amino intermediate which
5. customOrganic layer is separated
6. extractionThe aqueous layer is extracted twice with dichloromethane
7. extractionThe combined organic extracted
8. washare washed with citric acid (4 ml), sodium carbonate (6 ml) and brine
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customchromatographed with hexane/ethyl acetate from 5:1 to 1:1