3,4,5,6-Tetrahydrophthalic anhydride → 3-(3-Bromo-4-fluoro-benzylidene)-4,5,6,7-tetrahydro-3H-isobenzofuran-1-one

HRID 1012952Notes

Reaction equation

HRID 1012952 reaction equation
[C:1]1(=[O:11])[C:9]2[CH2:8][CH2:7][CH2:6][CH2:5][C:4]=2[C:3](=O)[O:2]1.[Br:12][C:13]1[CH:14]=[C:15]([CH2:20]C(O)=O)[CH:16]=[CH:17][C:18]=1[F:19].C([O-])(=O)C.[Na+]>>[Br:12][C:13]1[CH:14]=[C:15]([CH:16]=[CH:17][C:18]=1[F:19])[CH:20]=[C:3]1[C:4]2[CH2:5][CH2:6][CH2:7][CH2:8][C:9]=2[C:1](=[O:11])[O:2]1

Participants

4

Reactant 3

HCID 124753,4,5,6-Tetrahydrophthalic anhydrideHCID 517045Sodium AcetateHCID 34163393-Bromo-4-fluorophenylacetic Acid

Product 1

HCID 675241363-(3-Bromo-4-fluoro-benzylidene)-4,5,6,7-tetrahydro-3H-isobenzofuran-1-one

Procedure

4,5,6,7-tetrahydro-isobenzofuran-1,3-dione (7) (16.7 g, 109.7 mmol) and 3-bromo-4-fluorophenylacetic acid (15.0 g, 64.37 mmol) were heated in the presence of sodium acetate (0.259 g, 3.160 mmol) to 210° C. using a ‘Wood's Alloy’ bath for 4.5 hours. The reaction mixture was then poured into a crucible and cooled to give a crystalline solid. The solid was ground with a mortar and pestle and triturated with ethanol (20 ml). The resultant suspension was then filtered and washed with further ethanol (10 ml). The solid was then dried to afford the desired product as a mixture of geometric isomers. Main peak in LC-MS, (20.78 g, 94% purity) and required no further purification; m/z (LC-MS, ESP), RT=4.74 mins (no ionization observed).

Workup

  1. customfor 4.5 hours
  2. additionThe reaction mixture was then poured into a crucible and
  3. temperaturecooled
  4. customto give a crystalline solid
  5. customtriturated with ethanol (20 ml)
  6. filtrationThe resultant suspension was then filtered
  7. washwashed with further ethanol (10 ml)
  8. customThe solid was then dried

Sources & evidence

ORD record
ord-feca037d72c54cec85bcb025dd40f053
Source dataset
uspto-grants-2011_07
Patent number
US07981890B2

Reaction notes

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