Phthalic Anhydride → 2-(3-fluoro-4-methylphenyl)-1H-isoindole-1,3(2H)-dione

HRID 1861937

Reaction equation

HRID 1861937 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[CH3:9])[NH2:5].[C:10]1(=O)[O:15][C:13](=[O:14])[C:12]2=[CH:16][CH:17]=[CH:18][CH:19]=[C:11]12.C(N(CC)CC)C>C(Cl)(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([N:5]2[C:13](=[O:14])[C:12]3=[CH:16][CH:17]=[CH:18][CH:19]=[C:11]3[C:10]2=[O:15])[CH:6]=[CH:7][C:8]=1[CH3:9]

Participants

5

Reactant 3

HCID 6811Phthalic AnhydrideHCID 8471TriethylamineHCID 99573-Fluoro-4-methylaniline

Product 1

HCID 6833332-(3-fluoro-4-methylphenyl)-1H-isoindole-1,3(2H)-dioneYield 73.3%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A mixture of 3-fluoro-4-methylaniline (12.5 g), phthalic anhydride (17.8 g), triethylamine (27.9 ml) and chloroform (100 ml) was heated under reflux for 6 days and concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed successively with 2 N HCl and a saturated aqueous sodium chloride solution; the organic layer was then dried with anhydrous sodium sulfate and concentrated under reduced pressure. Subsequently, chloroform was added to the resulting residue and the insoluble matter was filtered off whereas the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent, chloroform methanol=98:2) to give 18.7 g of the titled compound (yield, 73%).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 6 days
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed successively with 2 N HCl
  6. dry with materialthe organic layer was then dried with anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. additionSubsequently, chloroform was added to the resulting residue
  9. filtrationthe insoluble matter was filtered off whereas the filtrate
  10. concentrationwas concentrated under reduced pressure
  11. customThe resulting residue was purified by silica gel column chromatography (eluent, chloroform methanol=98:2)

Sources & evidence

ORD record
ord-cc0864c902174e3a862fafb9e2138856
Source dataset
uspto-grants-2003_03
Patent number
US06534546B1

Linked notes

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