Reacción #43997

Ecuación de reacción

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

Rendimiento 15.0%

Disolventes

DMF

Acetic acid

carbon tetrachloride

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe mixture was heated
2. 2
   Temperaturaat reflux under nitrogen for 45 min
3. 3
   Otroilluminating with a 200 W lamp
4. 4
   Temperaturathe mixture refluxed for 3 h under nitrogen
5. 5
   Otrothe reaction evaporated to dryness under vacuum
6. 6
   OtroThe product was partially purified by SPE (NH2, 10 g)
7. 7
   Lavadoeluting with methanol
8. 8
   workup.ADDITIONThe fractions containing product
9. 9
   Lavadowashing with 5% acetic acid in methanol
10. 10
    OtroAfter evaporation of the solvents under vacuum
11. 11
    Lavadoeluting with a gradient (1:1 ethyl acetate/cyclohexane to 5% methanol, 1% acetic acid in 1:1 ethyl acetate/cyclohexane)

Procedimiento

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%).

Fuente