3,4,5,6-Tetrahydrophthalic anhydride → 1H-Isoindole-1,3(2H)-dione, 2-(4-chloro-2-fluoro-5-hydroxyphenyl)-4,5,6,7-tetrahydro-

HRID 1638897Notes

Reaction equation

HRID 1638897 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([NH2:9])=[CH:4][C:3]=1[OH:10].[C:11]1(=O)[O:16][C:14](=[O:15])[C:13]2[CH2:17][CH2:18][CH2:19][CH2:20][C:12]1=2>C(O)(=O)C>[Cl:1][C:2]1[C:3]([OH:10])=[CH:4][C:5]([N:9]2[C:14](=[O:15])[C:13]3[CH2:17][CH2:18][CH2:19][CH2:20][C:12]=3[C:11]2=[O:16])=[C:6]([F:8])[CH:7]=1

Participants

4

Reactant 2

HCID 124753,4,5,6-Tetrahydrophthalic anhydrideHCID 1586545-Amino-2-chloro-4-fluorophenol

Product 1

HCID 1586511H-Isoindole-1,3(2H)-dione, 2-(4-chloro-2-fluoro-5-hydroxyphenyl)-4,5,6,7-tetrahydro-Yield 34.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

2-Chloro-4-fluoro-5-aminophenol (6.6 g) and 3,4,5,6-tetrahydrophthalic anhydride (6 g) were dissolved in acetic acid (20 ml) and refluxed for 2 hours. The resultant mixture was allowed to cool to room temperature and poured into ice-water, followed by extraction with ether. The ether extract was washed with a saturated sodium hydrogen carbonate solution and water in order, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel chromatography to give 4.0 g of N-(4-chloro-2-fluoro-5-hydroxyphenyl)-3,4,5,6-tetrahydrophthalimide. M.P., 151° C.

Workup

  1. temperaturerefluxed for 2 hours
  2. extractionfollowed by extraction with ether
  3. extractionThe ether extract
  4. washwas washed with a saturated sodium hydrogen carbonate solution and water in order
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-98f80e55115e49d99154a665bdbe7951
Source dataset
uspto-grants-1989_11
Patent number
US04881970

Reaction notes

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