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

HRID 1836008Notes

Reaction equation

HRID 1836008 reaction equation
[OH:1][C:2]1[C:17]([CH:18]=[N:19]O)=[C:6]2[CH:7]=[C:8]([C:10]3[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=3)[O:9][C:5]2=[C:4]([O:21][CH3:22])[CH:3]=1.[H-].[Na+].[OH-].[Na+].Cl>CC(OC(C)=O)=O.CO>[OH:1][C:2]1[C:17]([C:18]#[N:19])=[C:6]2[CH:7]=[C:8]([C:10]3[CH:11]=[CH:12][C:13]([OH:16])=[CH:14][CH:15]=3)[O:9][C:5]2=[C:4]([O:21][CH3:22])[CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 1363978535-Hydroxy-2-(4-hydroxy-phenyl)-7-methoxy-benzofuran-4-carbaldehyde oxime

Product 1

HCID 101493935-Hydroxy-2-(4-hydroxy-phenyl)-7-methoxy-benzofuran-4-carbonitrile

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 7918Acetic AnhydrideSolvent

Conditions

Temperature
100 °C

Procedure

The crude 7 oxime 72 was heated in neat Ac2O at 100° C. for 30 minutes. The Ac2O was removed and the crude product was dissolved in EtOAc, washed with brine and dried over MgSO4. The solution was concentrated down and the crude triacetate was dissolved in DMF (10 mL) and treated with NaH (0.1 g, 60% dispersion in mineral oil, 2.5 mmol) and the reaction mixture was heated to 100° C. for 15 min. After cooling to rt, the solution was treated with a 20% NaOH aq solution and enough MeOH to get everything in one phase. This solution was then heated briefly (long enough to hydrolyze the acetates as determined by TLC analysis) and allowed to cool back to rt. The solution was acidifed with 2N HCl aq and the solution was extracted with EtOAc. The EtOAc extract was washed with NaHCO3 and brine and dried over MgSO4. The solution was filtered, concentrated and chromatographed on silica gel (2:8 to 4:6 EtOAc/hexanes) to yield 80 mg of the pdt nitrile 73 as a white solid: Mp=286-288° C.; 1H NMR (DMSO-d6) δ 10.9 (br s, 1 H), 9.98 (br s, 1 H), 7.77 (d, 2 H, J=8.7 Hz), 7.20 (s, 1 H), 6.87 (d, 2 H, J=8.7 Hz), 6.48 (s, 1 H), 3.97 (s, 3 H).

Workup

  1. customThe Ac2O was removed
  2. dissolutionthe crude product was dissolved in EtOAc
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. concentrationThe solution was concentrated down
  6. dissolutionthe crude triacetate was dissolved in DMF (10 mL)
  7. temperatureAfter cooling to rt
  8. customto get everything in one phase
  9. temperatureThis solution was then heated briefly (long enough
  10. temperatureto cool back to rt
  11. extractionthe solution was extracted with EtOAc
  12. extractionThe EtOAc extract
  13. washwas washed with NaHCO3 and brine
  14. dry with materialdried over MgSO4
  15. filtrationThe solution was filtered
  16. concentrationconcentrated
  17. customchromatographed on silica gel (2:8 to 4:6 EtOAc/hexanes)

Sources & evidence

ORD record
ord-4f4c5e44b7ba49d489aba06a3d0d42d3
Source dataset
uspto-grants-2004_08
Patent number
US06774248B2

Reaction notes

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