4-Aminobenzoic Acid → 4-(1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-4,7-methanoisoindol-2-yl)benzoic acid

HRID 1494621Notes

Reaction equation

HRID 1494621 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.CC(N(C)C)=O.C1(C)C=CC=CC=1.[CH:24]12[CH2:30][CH:27]([CH:28]=[CH:29]1)[CH:26]1[C:31]([O:33][C:34](=O)[CH:25]21)=[O:32]>O>[O:32]=[C:31]1[CH:26]2[CH:25]([CH:24]3[CH2:30][CH:27]2[CH:28]=[CH:29]3)[C:34](=[O:33])[N:1]1[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 9784-Aminobenzoic AcidHCID 1140TolueneHCID 13223826-62-0HCID 31374Dimethylacetamide

Product 1

HCID 5486924-(1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-4,7-methanoisoindol-2-yl)benzoic acidYield 94.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
165 °C

Procedure

To 4-aminobenzoic acid (800 g, 5.83 mol) is added dimethylacetamide (2.5 l), toluene (1 l), and slowly with stirring bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic anhydride (956 g, 5.83 mol). After the addition the mixture is stirred for 1 hour, raised to 140° C. with removal of water (100 ml) azeotropically and then raised to 165° C. to remove the toluene. The mixture is cooled and the product precipitated into water (3 l). Filtration, washing with water, drying in an oven at 80° C. and recrystallisation from ethanol yields a white crystalline solid (1.56 kg, 94%). M.p.: 224°-228° C.

Workup

  1. additionAfter the addition the mixture
  2. customto remove the toluene
  3. temperatureThe mixture is cooled
  4. customthe product precipitated into water (3 l)
  5. filtrationFiltration
  6. washwashing with water
  7. customdrying in an oven at 80° C.
  8. customrecrystallisation from ethanol

Sources & evidence

ORD record
ord-d3a8efd0c8b9494ebc1bfc8142b95f30
Source dataset
uspto-grants-1991_06
Patent number
US05026871

Reaction notes

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