Reaktion #43997

Reaktionsgleichung

Sodium metabisulphite

4-aminophenyl acetic acid

triethylamine

ethyl 1,4-dimethoxy-2-methylnaphthalene-3-carboxylate

N-bromosuccinimide

dibenzylperoxide

→

[4-(4,9-dimethoxy-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl)phenyl]acetic acid

Ausbeute 15.0%

Lösungsmittel

DMF

Acetic acid

carbon tetrachloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture was heated
2. 2
   Temperaturat reflux under nitrogen for 45 min
3. 3
   Sonstigeilluminating with a 200 W lamp
4. 4
   Temperaturthe mixture refluxed for 3 h under nitrogen
5. 5
   Sonstigethe reaction evaporated to dryness under vacuum
6. 6
   SonstigeThe product was partially purified by SPE (NH2, 10 g)
7. 7
   Wascheneluting with methanol
8. 8
   workup.ADDITIONThe fractions containing product
9. 9
   Waschenwashing with 5% acetic acid in methanol
10. 10
    SonstigeAfter evaporation of the solvents under vacuum
11. 11
    Wascheneluting with a gradient (1:1 ethyl acetate/cyclohexane to 5% methanol, 1% acetic acid in 1:1 ethyl acetate/cyclohexane)

Vorschrift

To a solution of ethyl 1,4-dimethoxy-2-methylnaphthalene-3-carboxylate (73 mg, 0.266 mmol) in carbon tetrachloride (10 ml) was added N-bromosuccinimide (47 mg, 0.266 mmol) and dibenzylperoxide (5 mg). The mixture was heated at reflux under nitrogen for 45 min, illuminating with a 200 W lamp. The reaction was cooled to room temperature, 4-aminophenyl acetic acid (40 mg, 0.266 mmol), triethylamine (74 μl, 0.53 mmol) and DMF (5 ml) added and the reaction stirred for 48 h. Acetic acid (glacial, 1 ml) was added to the reaction and the mixture refluxed for 3 h under nitrogen. Sodium metabisulphite solution (1 ml) was added and the reaction evaporated to dryness under vacuum. The product was partially purified by SPE (NH2, 10 g) eluting with methanol then 5% acetic acid in methanol. The fractions containing product were passed through a silica plug washing with 5% acetic acid in methanol. After evaporation of the solvents under vacuum, the residue was columned on a silica gel flash column eluting with a gradient (1:1 ethyl acetate/cyclohexane to 5% methanol, 1% acetic acid in 1:1 ethyl acetate/cyclohexane) to give [4-(4,9-dimethoxy-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl)phenyl]acetic acid (15 mg, 15%).

Quelle