Triethylamine → 2-{(E)-2-[3-amino-5-(trifluoromethyl)phenyl]vinyl}-1H-isoindole-1,3(2H)-dione

HRID 1640127Notes

Reaction equation

HRID 1640127 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1)[NH2:5].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.CCN(CC)CC.[CH:42]([N:44]1[C:52](=[O:53])[C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[C:45]1=[O:54])=[CH2:43]>C(C#N)(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:5][C:4]1[CH:3]=[C:2](/[CH:43]=[CH:42]/[N:44]2[C:45](=[O:54])[C:46]3[C:51](=[CH:50][CH:49]=[CH:48][CH:47]=3)[C:52]2=[O:53])[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 770351H-Isoindole-1,3(2H)-dione, 2-ethenyl-HCID 80271Tri-o-tolylphosphineHCID 27358803-Bromo-5-(trifluoromethyl)aniline

Product 1

HCID 591349702-{(E)-2-[3-amino-5-(trifluoromethyl)phenyl]vinyl}-1H-isoindole-1,3(2H)-dioneYield 28.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 694302-OxopropiononitrileSolvent

Procedure

3-Bromo-5-(trifluoromethyl)aniline (5.00 g, 0.0208 mol) was dissolved in AcCN (200 mL) and the solution was degassed with N2. Pd(OAc)2 (230 mg, 1.02 mmol), tris(2-methylphenyl)phosphine (630 mg, 2.07 mmol), and Et3N (5.75 mL, 0.041 mol) were added and the bright orange solution was allowed to stir at rt for 1 h. To this solution was added 2-vinyl-1H-isoindole-1,3(2H)-dione (3.61 g, 0.021 mol) and the reaction mixture was degassed and heated at reflux for 16 h. The reaction was filtered through Celite. The filtrate was washed with water and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give 2-{(E)-2-[3-amino-5-(trifluoromethyl)phenyl]vinyl}-1H-isoindole-1,3(2H)-dione (1.99 g, 24% yield). LCMS: (FA) ES+ 334.

Workup

  1. customthe solution was degassed with N2
  2. customthe reaction mixture was degassed
  3. temperatureheated
  4. temperatureat reflux for 16 h
  5. filtrationThe reaction was filtered through Celite
  6. washThe filtrate was washed with water and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-79106a2bcccd4829a711477cc07df78d
Source dataset
uspto-grants-2012_02
Patent number
US08110687B2

Reaction notes

Loading…