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

HRID 15719

Reaction equation

HRID 15719 reaction equation
[CH3:1][O:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([O:13][CH3:14])=[C:5]([C:15]([O:17]CC)=O)[C:4]=1[CH3:20].BrN1C(=O)CCC1=O.C(OOCC1C=CC=CC=1)C1C=CC=CC=1.[NH2:45][C:46]1[CH:51]=[CH:50][C:49]([CH2:52][C:53]([OH:55])=[O:54])=[CH:48][CH:47]=1.C(N(CC)CC)C.S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+]>C(Cl)(Cl)(Cl)Cl.C(O)(=O)C.CN(C=O)C>[CH3:1][O:2][C:3]1[C:4]2[CH2:20][N:45]([C:46]3[CH:47]=[CH:48][C:49]([CH2:52][C:53]([OH:55])=[O:54])=[CH:50][CH:51]=3)[C:15](=[O:17])[C:5]=2[C:6]([O:13][CH3:14])=[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=12

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 145334-Aminophenylacetic acidHCID 67184N-bromobutanimideHCID 656671Sodium PyrosulfiteHCID 11229634Benzyl PeroxideHCID 11369352Ethyl 1,4-dimethoxy-3-methyl-2-naphthoate

Product 1

HCID 9864500[4-(4,9-dimethoxy-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2-yl)phenyl]acetic acidYield 15%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 5943Carbon TetrachlorideSolventHCID 6228DimethylformamideSolvent

Procedure

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%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux under nitrogen for 45 min
  3. customilluminating with a 200 W lamp
  4. temperaturethe mixture refluxed for 3 h under nitrogen
  5. customthe reaction evaporated to dryness under vacuum
  6. customThe product was partially purified by SPE (NH2, 10 g)
  7. washeluting with methanol
  8. additionThe fractions containing product
  9. washwashing with 5% acetic acid in methanol
  10. customAfter evaporation of the solvents under vacuum
  11. washeluting with a gradient (1:1 ethyl acetate/cyclohexane to 5% methanol, 1% acetic acid in 1:1 ethyl acetate/cyclohexane)

Sources & evidence

ORD record
ord-75b8ec8489e648b0ae41eabd693a6b21
Source dataset
uspto-grants-2010_06
Patent number
US07732622B2

Linked notes

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