Ethyl Acrylate → (E)-ethyl 3-(5-bromopyrazin-2-yl)acrylate

HRID 508661Notes

Reaction equation

HRID 508661 reaction equation
Br[C:2]1[CH:7]=[N:6][C:5]([Br:8])=[CH:4][N:3]=1.[C:9]([O:13][CH2:14][CH3:15])(=[O:12])[CH:10]=[CH2:11].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CN(C=O)C.C(N(C(C)C)CC)(C)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Br:8][C:5]1[N:6]=[CH:7][C:2](/[CH:11]=[CH:10]/[C:9]([O:13][CH2:14][CH3:15])=[O:12])=[N:3][CH:4]=1

Participants

7

Reactant 3

HCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 114704212,5-dibromopyrazine

Product 1

HCID 53259408(E)-ethyl 3-(5-bromopyrazin-2-yl)acrylateYield 8.6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 81531DiisopropylethylamineSolvent

Conditions

Temperature
115 °C

Procedure

A solution of 2,5-dibromopyrazine (238.0 mg, 1.0 mmol), ethyl acrylate (174.0 μL, 1.6 mmol), palladium(II) acetate (3.4 mg, 0.015 mmol), and tri(o-tolyl)phosphine (36.5 mg, 0.12 mmol) in DMF (1.4 mL) and diisopropylethylamine (0.7 mL) was heated at reflux (115° C. oil bath) for 4.4 h, cooled to room temperature, and then quenched with H2O. The suspension was extracted with EtOAc (300 mL). The extract was washed (brine) and dried. After solvent removal at reduced pressure, the residue was purified on silica gel (11% EtOAc/hexane) to give 22 mg (8.5%) of ethyl(E)-3-(5-bromo-2-pyrazinyl)-2-propenoate as a cream solid.

Workup

  1. temperaturecooled to room temperature
  2. customquenched with H2O
  3. extractionThe suspension was extracted with EtOAc (300 mL)
  4. washThe extract was washed (brine)
  5. customdried
  6. customAfter solvent removal at reduced pressure
  7. customthe residue was purified on silica gel (11% EtOAc/hexane)

Sources & evidence

ORD record
ord-f54a490d4cb44016b7176c0e9685e28d
Source dataset
uspto-grants-2015_08
Patent number
US09096544B2

Reaction notes

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