Ethyl Acrylate → (E)-ethyl 3-(2-amino-5-bromophenyl)acrylate

HRID 1504459Notes

Reaction equation

HRID 1504459 reaction equation
[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4](I)[CH:3]=1.[C:10]([O:14][CH2:15][CH3:16])(=[O:13])[CH:11]=[CH2:12].C(=O)(O)[O-].[Na+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:6][C:5]1[CH:7]=[CH:8][C:2]([Br:1])=[CH:3][C:4]=1/[CH:12]=[CH:11]/[C:10]([O:14][CH2:15][CH3:16])=[O:13]

Participants

6

Reactant 3

HCID 8821Ethyl AcrylateHCID 516892Sodium BicarbonateHCID 8239344-Bromo-2-iodoaniline

Product 1

HCID 86278419(E)-ethyl 3-(2-amino-5-bromophenyl)acrylateYield 91.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 4-bromo-2-iodoaniline (750 g, 2.51 mol, 1.0 equiv) in DMF (5.0 L) was added ethyl acrylate (277 g, 2.76 mol, 1.1 equiv, Avra) and sodium bicarbonate (680 g, 6.29 mol, 2.5 equiv). The reaction mixture was degassed with nitrogen for 20 min followed by the addition of palladium acetate (28.8 g, 128.27 mmol, 0.05 equiv, Hindustan Platinum). The reaction mixture was heated at 70° C. for 3 h. The reaction was filtered through celite and the celite bed was washed with ethyl acetate (2×500 mL). The filtrate was concentrated under reduced pressure to obtain the crude residue which was purified by column chromatography (silica gel; mesh size 60-120, elution 0-20% ethyl acetate in hexanes) to obtain (E)-ethyl 3-(2-amino-5-bromophenyl)acrylate (620 g, 77.0%), as yellow solid. TLC solvent system: 20% ethyl acetate in hexanes. Product's Rf: 0.4. MS (ESI, positive ion) m/z; 270.2 (M+1). 1H NMR (400 MHz, DMSO) δ 7.75 (d, J=16.1 Hz, 1H), 7.57 (d, J=2.0 Hz, 1H), 7.16 (dd, J=9.1, 2.4 Hz, 1H), 6.66 (d, J=8.6 Hz, 1H), 6.43 (d, J=8.6 Hz, 1H), 5.81 (s, 2H), 4.20 (q, J=7.2 Hz, 2H), 1.27 (t, J=7.2 Hz, 3H).

Workup

  1. customThe reaction mixture was degassed with nitrogen for 20 min
  2. filtrationThe reaction was filtered through celite
  3. washthe celite bed was washed with ethyl acetate (2×500 mL)
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customto obtain the crude residue which
  6. customwas purified by column chromatography (silica gel; mesh size 60-120, elution 0-20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-e336c656f1d84bdb828f6edbb08f17f5
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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