Acetic Anhydride → 2-(4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)phenyl)acetic acid

HRID 485271Notes

Reaction equation

HRID 485271 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.[C:12]1(=O)[O:17][C:15](=[O:16])[CH:14]=[CH:13]1.C([O-])(=O)C.[Na+].C(OC(=O)C)(=O)C>CN(C=O)C>[C:12]1(=[O:17])[N:1]([C:2]2[CH:3]=[CH:4][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[CH:6][CH:7]=2)[C:15](=[O:16])[CH:14]=[CH:13]1

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 7923Maleic AnhydrideHCID 145334-Aminophenylacetic acidHCID 517045Sodium Acetate

Product 1

HCID 167808472-(4-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)phenyl)acetic acidYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

According to the method of M. P. Cava, A. A. Deana, K. Muth and M. J. Mitchell (Org. Synth., Coll. Vol. 5, 944 (1973)), 40 ml of a solution of 10 g (66.2 mmols) of 4-aminophenylacetic acid in DMF was added to 15 ml of a solution of 7.14 g (72.8 mmols) of maleic anhydride in DMF at room temperature in argon atmosphere. The reaction mixture was stirred at room temperature for 3 hours and then diluted with 250 ml of ether-benzene (1:1). The resulting precipitate was filtered off, with which 2.87 g (35 mmols) of sodium acetate and 70 ml of acetic anhydride were admixed. The mixture was stirred at 100° C. for 1 hour in argon atmosphere and concentrated in a vacuum. The residue was diluted with 300 ml of ethyl acetate. The ethyl acetate layer was washed with saturated sodium chloride aqueous solution, dried over Na2SO4, concentrated and thereafter subjected to silica gel column chromatography (90:10:5 chloroform-ethyl acetate-acetic acid to 50:50:5 chloroform-ethyl acetate-acetic acid), giving 8.72 g (yield 57%) of (4-maleimidophenyl)acetic acid in the form of a white solid.

Workup

  1. stirringThe mixture was stirred at 100° C. for 1 hour in argon atmosphere
  2. concentrationconcentrated in a vacuum
  3. additionThe residue was diluted with 300 ml of ethyl acetate
  4. washThe ethyl acetate layer was washed with saturated sodium chloride aqueous solution
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-8447048226d44f8393781406c5ddab51
Source dataset
uspto-grants-1985_08
Patent number
US04536391

Reaction notes

Loading…