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 1086664Notes

Reaction equation

HRID 1086664 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 this order, dried over anhydrous magnesium sulfate was concentrated. The residue was purified by silica gel chromatography to obtain 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 this order
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationwas concentrated
  7. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-20d13e2c157a456a9772bb1aceb17152
Source dataset
uspto-grants-1991_07
Patent number
US05030760

Reaction notes

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