Réaction #43997

Équation de réaction

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

Rendement 15.0%

Solvants

DMF

Acetic acid

carbon tetrachloride

Conditions de réaction

Traitement

1. 1
   TempératureThe mixture was heated
2. 2
   Températureat reflux under nitrogen for 45 min
3. 3
   Autreilluminating with a 200 W lamp
4. 4
   Températurethe mixture refluxed for 3 h under nitrogen
5. 5
   Autrethe reaction evaporated to dryness under vacuum
6. 6
   AutreThe product was partially purified by SPE (NH2, 10 g)
7. 7
   Lavageeluting with methanol
8. 8
   workup.ADDITIONThe fractions containing product
9. 9
   Lavagewashing with 5% acetic acid in methanol
10. 10
    AutreAfter evaporation of the solvents under vacuum
11. 11
    Lavageeluting with a gradient (1:1 ethyl acetate/cyclohexane to 5% methanol, 1% acetic acid in 1:1 ethyl acetate/cyclohexane)

Mode opératoire

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%).

Source