Ethyl Acrylate → ethyl(2E)-3-(4-amino-2-fluorophenyl)acrylate

HRID 507916Notes

Reaction equation

HRID 507916 reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[F:9].[C:10]([O:14][CH2:15][CH3:16])(=[O:13])[CH:11]=[CH2:12].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(N(CC)C(C)C)(C)C.CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:6][C:5]1[CH:7]=[CH:8][C:2](/[CH:12]=[CH:11]/[C:10]([O:14][CH2:15][CH3:16])=[O:13])=[C:3]([F:9])[CH:4]=1

Participants

7

Reactant 3

HCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 8218484-Bromo-3-fluoroaniline

Product 1

HCID 20536506ethyl(2E)-3-(4-amino-2-fluorophenyl)acrylateYield 96%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 81531DiisopropylethylamineSolvent

Conditions

Temperature
110 °C

Procedure

4-Bromo-3-fluoroaniline (13.3 g, 70.0 mmol), ethyl acrylate (9.48 mL, 87.5 mmol) and tris(2-methylphenyl)phosphine (8.52 g, 28.0 mmol) were dissolved in N,N-diisopropylethylamine (50 mL) and N,N-dimethylformamide (50 mL), palladium(II) acetate (0.786 g, 3.50 mmol) was added, and the mixture was stirred under an argon atmosphere at 110° C. for 5 hr. After cooling the reaction mixture, the solvent was evaporated under reduced pressure. Water and ethyl acetate were added to the residue, and the insoluble material was removed by filtering through celite. The organic layer in the filtrate was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (20%-60% ethyl acetate/hexane) to give the title compound (14.0 g, yield 96%). A part thereof was recrystallized to give yellow prism crystals.

Workup

  1. temperatureAfter cooling the reaction mixture
  2. customthe solvent was evaporated under reduced pressure
  3. additionWater and ethyl acetate were added to the residue
  4. customthe insoluble material was removed
  5. filtrationby filtering through celite
  6. washThe organic layer in the filtrate was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (20%-60% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-0ce3e775f2064b1d9ecdac16989cae66
Source dataset
uspto-grants-2010_08
Patent number
US07786165B2

Reaction notes

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