Hydrochloric Acid → 5-Hydroxy-2-(4-hydroxy-phenyl)-7-methoxy-benzofuran-4-carbaldehyde

HRID 1836006Notes

Reaction equation

HRID 1836006 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[C:16]([O:17][CH3:18])=[CH:15][C:14]([OH:19])=[CH:13][C:11]=3[CH:12]=2)=[CH:4][CH:3]=1.O=P(Cl)(Cl)Cl.[OH-].[Na+].Cl.[C:28]([O-])(O)=[O:29].[Na+]>CN(C=O)C>[OH:19][C:14]1[C:13]([CH:28]=[O:29])=[C:11]2[CH:12]=[C:8]([C:5]3[CH:4]=[CH:3][C:2]([OH:1])=[CH:7][CH:6]=3)[O:9][C:10]2=[C:16]([O:17][CH3:18])[CH:15]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 102860222-(4-Hydroxy-phenyl)-7-methoxy-benzofuran-5-ol

Product 1

HCID 101494185-Hydroxy-2-(4-hydroxy-phenyl)-7-methoxy-benzofuran-4-carbaldehyde

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 62 (0.25 g, 1.0 mmol) in DMF (20 mL) was treated with POCl3 (1 mL, 11 mmol) and heated at 80° C.-100° C. for 15 minutes. The reaction mixture was worked up by allowing to cool and then poured into crushed ice. 2N NaOH aq was added and the solution stirred for several minutes and then the mixture was acidified with 2N HCl aq and then neutralized with NaHCO3 aq. The mixture was then extracted with EtOAc and washed with brine, dried over MgSO4, filtered, concentrated and chromatographed on silica gel (2:8 to 4:6 EtoAc/hexanes) to yield a solid which still contained some starting material, but that was purified by trituration with EtOAc to yield 47 mg the desired pdt as a white solid: Mp=254-255° C.; 1H NMR (DMSO-d6) δ 10.29 (s, 1 H), 10.0 (br s, 1 H), 7.73 (d, 2 H, J=8.7 Hz), 7.59 (s, 1 H), 6.88 (d, 2 H, J=8.7 Hz), 6.46 (s, 1 H), 4.00 (s, 3 H); MS 281 (M−H)−.

Workup

  1. temperatureheated at 80° C.-100° C. for 15 minutes
  2. temperatureto cool
  3. additionpoured
  4. custominto crushed ice
  5. extractionwas then extracted with EtOAc
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customchromatographed on silica gel (2:8 to 4:6 EtoAc/hexanes)
  11. customto yield a solid which
  12. customthat was purified by trituration with EtOAc
  13. customto yield 47 mg the desired pdt as a white solid

Sources & evidence

ORD record
ord-7a9018c790f2478489264cbccd762756
Source dataset
uspto-grants-2004_08
Patent number
US06774248B2

Reaction notes

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