반응 #221013

반응 방정식

[4-(1-Ethoxymethyl-1H-imidazol-2-yl)-1-isopropyl-3-methyl-4-oxo-but-2-enyl]-methyl-carbamic acid tert-butyl ester

2-tert-Butoxycarbonylamino-3,3-dimethyl-butyric acid

3-(diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one

triethylamine

→

(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

용매

dichloromethane water

hydrochloric acid dioxane

dichloromethane

반응 조건

후처리

1. 1
   기타The solvent is removed in vacuo
2. 2
   workup.ADDITIONDichloromethane is added to the residue
3. 3
   기타evaporated (this step
4. 4
   기타to give a white solid amino intermediate which
5. 5
   기타Organic layer is separated
6. 6
   추출The aqueous layer is extracted twice with dichloromethane
7. 7
   추출The combined organic extracted
8. 8
   세척are washed with citric acid (4 ml), sodium carbonate (6 ml) and brine
9. 9
   건조dried over sodium sulfate
10. 10
    여과filtered
11. 11
    농축concentrated in vacuo
12. 12
    기타chromatographed with hexane/ethyl acetate from 5:1 to 1:1

실험 절차

[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

출처