Hydrochloric Acid → 3-[5-Hydroxy-2-(4-hydroxyphenyl)-benzofuran-7-yl]-acrylamide

HRID 1836000Notes

Reaction equation

HRID 1836000 reaction equation
Br[C:2]1[C:10]2[O:9][C:8]([C:11]3[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=3)=[CH:7][C:6]=2[CH:5]=[C:4]([OH:18])[CH:3]=1.[C:19]([NH2:23])(=[O:22])[CH:20]=[CH2:21].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.Cl>C(N(CC)CC)C.C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[OH:18][C:4]1[CH:3]=[C:2]([CH:21]=[CH:20][C:19]([NH2:23])=[O:22])[C:10]2[O:9][C:8]([C:11]3[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=3)=[CH:7][C:6]=2[CH:5]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6579AcrylamideHCID 80271Tri-o-tolylphosphineHCID 102863527-Bromo-2-(4-hydroxy-phenyl)-benzofuran-5-ol

Product 1

HCID 688451963-[5-Hydroxy-2-(4-hydroxyphenyl)-benzofuran-7-yl]-acrylamideYield 51.8%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 7-bromo-2-(4-hydroxy-phenyl)-benzofuran-5-ol 58 (0.3 g, 0.98 mmol) in triethylamine (5 mL) and acetonitrile (5 mL) was added acrylamide (0.077 g, 1.08 mmol) and tri-(o-tolyl) phosphine (0.060 g, 0.2 mmol). This mixture was purged with nitrogen for 10 minutes. Then palladium (II) acetate (0.022 g, 0.098 mmol) was added and the reaction was heated at reflux for 3.5 hours. To the cooled reaction was added 2N HCl and the product was extracted into ethyl acetate. The organic layer was washed with brine, dried over MgSO4 and the solvent removed in vacuo. The residue was purified via flash chromatography on silica gel, eluting with 10% methanol in dichloromethane to give 0.15 g of 3-[5-hydroxy-2-(4-hydroxyphenyl)-benzofuran-7-yl]-acrylamide 61: Mp=275° C. (dec); 1H NMR (DMSO-d6) δ 9.89 (s, 1 H), 9.35 (s, 1 H), 7.86 (br s, 1 H), 7.83 (d, 2 H, J=8.6 Hz), 7.53 (d, 1 H, J=15.9 Hz), 7.23 (br s, 1 H), 7.11 (s, 1 H), 7.04 (d, 1 H, J=15.9 Hz), 6.94 (d, 1 H, J=2.4 Hz), 6.90 (d, 2 H, 8.7 Hz), 6.83 (d, 1 H, J=2.3 Hz); MS 296 (M+H)+

Workup

  1. customThis mixture was purged with nitrogen for 10 minutes
  2. temperaturethe reaction was heated
  3. temperatureat reflux for 3.5 hours
  4. customTo the cooled reaction
  5. extractionthe product was extracted into ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. customthe solvent removed in vacuo
  9. customThe residue was purified via flash chromatography on silica gel
  10. washeluting with 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-54111cafc066416ea9596c8ad5068453
Source dataset
uspto-grants-2004_08
Patent number
US06774248B2

Reaction notes

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