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

HRID 1691530Notes

Reaction equation

HRID 1691530 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>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O>[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 4

HCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 8218484-Bromo-3-fluoroaniline

Product 1

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

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of 4-bromo-3-fluoroaniline (13.3 g, 70.0 mmol), ethyl acrylate (9.48 mL, 87.5 mmol), tris(2-methylphenyl)phosphine (8.52 g, 28.0 mmol), N,N-diisopropylethylamine (50 mL) and N,N-dimethylformamide (50 mL) was added palladium(II) acetate (0.786 g, 3.50 mmol), and the mixture was stirred at 110° C. for 5 hr under an argon atmosphere. The reaction mixture was cooled, and the solvent was evaporated under reduced pressure. Water and ethyl acetate were added to the residue, and the insoluble material was filtered off through celite. The filtrate was separated into the aqueous layer and the organic layer. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=20:80-60:40) to give the title compound (14.0 g, yield 96%). A part thereof was recrystallized to give yellow prisms.

Workup

  1. temperatureThe reaction mixture was cooled
  2. customthe solvent was evaporated under reduced pressure
  3. additionWater and ethyl acetate were added to the residue
  4. filtrationthe insoluble material was filtered off through celite
  5. customThe filtrate was separated into the aqueous layer
  6. washThe organic layer 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 (ethyl acetate:hexane=20:80-60:40)

Sources & evidence

ORD record
ord-cf911990dea34769a75ea450d45865bd
Source dataset
uspto-grants-2012_04
Patent number
US08153694B2

Reaction notes

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