3,4,5,6-Tetrahydrophthalic anhydride → 2-(2-Fluoro-4-hydroxyphenyl)-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione

HRID 257354Notes

Reaction equation

HRID 257354 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[F:9].[C:10]1(=O)[O:15][C:13](=[O:14])[C:12]2[CH2:16][CH2:17][CH2:18][CH2:19][C:11]1=2>>[F:9][C:3]1[CH:4]=[C:5]([OH:8])[CH:6]=[CH:7][C:2]=1[N:1]1[C:13](=[O:14])[C:12]2[CH2:16][CH2:17][CH2:18][CH2:19][C:11]=2[C:10]1=[O:15]

Participants

3

Reactant 2

HCID 124753,4,5,6-Tetrahydrophthalic anhydrideHCID 27359194-Amino-3-fluorophenol

Product 1

HCID 36139472-(2-Fluoro-4-hydroxyphenyl)-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione

Procedure

The filtrate from Step A was mixed with 9.74 g (0.0640 mole) of 3,4,5,6-tetrahydrophthalic anhydride, and the mixture was heated at reflux for approximately 64 hours. At the end of this period, the dark brown solution was poured over ice and extracted in succession with ethyl acetate and diethyl ether. The extracts were combined, washed with water, dried over anhydrous magnesium sulfate, and filtered. The solvents were evaporated under reduced pressure from the filtrate, leaving a dark brown oil as residue. This was placed on a silica gel column and eluted with methylene chloride/ethyl acetate (95/5). After the product-containing fractions were combined and the solvents evaporated under reduced pressure, 14.71 g of N-(2-fluoro-4-hydroxyphenyl)-3,4,5,6-tetrahydrophthalimide was recovered as an orange solid, m.p. 132°-136° C. The NMR spectrum was consistent with the proposed structure.

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for approximately 64 hours
  3. additionAt the end of this period, the dark brown solution was poured over ice
  4. extractionextracted in succession with ethyl acetate and diethyl ether
  5. washwashed with water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customThe solvents were evaporated under reduced pressure from the filtrate
  9. customleaving a dark brown oil as residue
  10. washeluted with methylene chloride/ethyl acetate (95/5)
  11. customthe solvents evaporated under reduced pressure, 14.71 g of N-(2-fluoro-4-hydroxyphenyl)-3,4,5,6-tetrahydrophthalimide
  12. customwas recovered as an orange solid, m.p. 132°-136° C

Sources & evidence

ORD record
ord-1acc133ea1fc404099bc5284d54ff9da
Source dataset
uspto-grants-1993_11
Patent number
US05262390

Reaction notes

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