Hydrochloric Acid → 3-[5-Hydroxy-2-(4-hydroxy-phenyl)benzofuran-7-yl]-acrylic acid methyl ester

HRID 1835998Notes

Reaction equation

HRID 1835998 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]([O:23][CH3:24])(=[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>[CH3:24][O:23][C:19](=[O:22])[CH:20]=[CH:21][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

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7294Methyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 102863527-Bromo-2-(4-hydroxy-phenyl)-benzofuran-5-ol

Product 1

HCID 688433923-[5-Hydroxy-2-(4-hydroxy-phenyl)benzofuran-7-yl]-acrylic acid methyl esterYield 15.6%

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 (1.0 g, 3.3 mmol) in triethylamine (10 mL) and acetonitrile (10 mL) was added methyl acrylate (0.44 mL, 4.9 mmol) and tri-(o-toly) phosphine (0.2 g, 0.66 mmol). This mixture was purged with nitrogen for 10 minutes. Then palladium (II) acetate (0.037 g, 0.17 mmol) was added and the reaction was heated at reflux for 4 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 22-50% ethyl acetate in hexane to give 0.16 g of 59: Mp=231-234° C.; 1H NMR (DMSO-d6) δ 9.93 (s, 1 H), 9.44 (s, 1 H), 7.80 (d, 1H, J=16.1 Hz), 7.72 (d, 2 H, J=8.6 Hz), 7.13 (s, 1 H), 7.02 (d, 1H, J=2.3 Hz), 6.98 (d, 1 H, J=2.3 Hz), 6.93 (d, 1 H, J=16.2 Hz), 6.92 (d, 2 H, J=8.6 Hz) 3.79 (s, 3 H); MS 311 (M+H)+

Workup

  1. customThis mixture was purged with nitrogen for 10 minutes
  2. temperaturethe reaction was heated
  3. temperatureat reflux for 4 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 22-50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-4eb7ccc2c1104542852b92ed9fc21fc7
Source dataset
uspto-grants-2004_08
Patent number
US06774248B2

Reaction notes

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