Triethylamine → Ethyl (E)-3-(4-Amino-6-bromo-3-pyridyl)acrylate

HRID 523080Notes

Reaction equation

HRID 523080 reaction equation
[NH2:1][C:2]1[C:7](I)=[CH:6][N:5]=[C:4]([Br:9])[CH:3]=1.[C:10]([O:14][CH2:15][CH3:16])(=[O:13])[CH:11]=[CH2:12].C(N(CC)CC)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>[NH2:1][C:2]1[CH:3]=[C:4]([Br:9])[N:5]=[CH:6][C:7]=1/[CH:12]=[CH:11]/[C:10]([O:14][CH2:15][CH3:16])=[O:13]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 8821Ethyl AcrylateHCID 601457042-Bromo-5-iodopyridin-4-amine

Product 1

HCID 89995588Ethyl (E)-3-(4-Amino-6-bromo-3-pyridyl)acrylateYield 89.6%

Reagents, catalysts & solvents 3

HCID 80271Tri-o-tolylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

4-Amino-2-bromo-5-iodopyridine (9.0 g 30.0 mmole) was dissolved in DMF (90 mL) and ethyl acrylate (6.5 mL, 60 mmole), triethylamine (6.1 mL, 43.2 mmole), tri-o-tolylphosphine (728 mg 2.4 mmole) and palladium acetate (270 mg 1.2 mmole) were added. The reaction was placed under nitrogen and heated at 100° C. for 3 hours. The reaction was concentrated in vacuo and diluted with EtOAc (250 mL). Water (100 mL) was added and the biphasic mixture filtered through celite. The filter cake was washed with EtOAc and the organic layers collected. The combined organic layers were washed with water (2×100 mL), brine, dried over sodium sulphate and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with a gradient of 10-40% EtOAc in DCM to afford the title compound (7.29 g, 89%).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. additiondiluted with EtOAc (250 mL)
  3. additionWater (100 mL) was added
  4. filtrationthe biphasic mixture filtered through celite
  5. washThe filter cake was washed with EtOAc
  6. customthe organic layers collected
  7. washThe combined organic layers were washed with water (2×100 mL), brine
  8. dry with materialdried over sodium sulphate
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified
  11. washeluting with a gradient of 10-40% EtOAc in DCM

Sources & evidence

ORD record
ord-80b24a51172c4ff59352cb27ca2abd1c
Source dataset
uspto-grants-2016_05
Patent number
US09334286B2

Reaction notes

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