Reaktion #221013

Reaktionsgleichung

[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

Lösungsmittel

dichloromethane water

hydrochloric acid dioxane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe solvent is removed in vacuo
2. 2
   workup.ADDITIONDichloromethane is added to the residue
3. 3
   Sonstigeevaporated (this step
4. 4
   Sonstigeto give a white solid amino intermediate which
5. 5
   SonstigeOrganic layer is separated
6. 6
   ExtraktionThe aqueous layer is extracted twice with dichloromethane
7. 7
   ExtraktionThe combined organic extracted
8. 8
   Waschenare washed with citric acid (4 ml), sodium carbonate (6 ml) and brine
9. 9
   Trocknendried over sodium sulfate
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated in vacuo
12. 12
    Sonstigechromatographed with hexane/ethyl acetate from 5:1 to 1:1

Vorschrift

[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

Quelle