Hydroxyamine hydrochloride → 1-[5-Hydroxy-2-(4-hydroxy-phenyl)-benzofuran-3-yl]-ethanone oxime

HRID 1836035Notes

Reaction equation

HRID 1836035 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10]3[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=3)=[C:7]([C:17](=O)[CH3:18])[C:6]=2[CH:20]=1.[NH2:21][OH:22].Cl>CCO.N1C(=O)CC[C@H]1C(O)=O>[OH:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10]3[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=3)=[C:7]([C:17](=[N:21][OH:22])[CH3:18])[C:6]=2[CH:20]=1

Participants

4

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 222216281-[5-Hydroxy-2-(4-hydroxy-phenyl)-benzofuran-3-yl]-ethanone

Product 1

HCID 1371789481-[5-Hydroxy-2-(4-hydroxy-phenyl)-benzofuran-3-yl]-ethanone oximeYield 6.5%

Reagents, catalysts & solvents 1

HCID 131724523EtOH PyrSolvent

Procedure

Ketone 110 (1.9 g, 7.1 mmol) was dissolved in a solution of EtOH/Pyr (50 mL/10 mL) and treated with NH2OH—HCl (0.5 g, 7.2 mmol) and heated at reflux until all of the starting material was consumed by TLC analysis. The reaction was worked up by concentrating down and partitioning the residue between EtOAc and 2 N HCl aq, washing the EtOAc layer with saturated NaHCO3 aq, brine and drying over MgSO4. The solution was then filtered, concentrated and chromatographed on silica gel (1:4 EtOAc/hexanes) and the product obtained triturated with CH2Cl2 to yield 0.131 g of the pure oxime. Stereochemistry of the oxime was tentatively defined as cis since no NOE effect between the oxime hydroxyl proton and the adjacent methyl group could be observed: Mp=217° C.; 1H NMR (DMSO-d6) δ 11.27 (s, 1 H), 9.94 (br s, 1 H), 9.23 (br s, 1 H), 7.51 (d, 2 H, J=8.8 Hz), 7.36 (d, 1 H, J=8.3 Hz), 7.03 (d, 1 H, J=2.4 Hz), 6.88 (d, 2 H, J=8.8 Hz), 6.74 (dd, 1 H, J=8.8 Hz, 2.4 Hz), 1.99 (s, 3 H).

Workup

  1. temperatureheated
  2. temperatureat reflux until all of the starting material
  3. customwas consumed by TLC analysis
  4. concentrationby concentrating down
  5. custompartitioning the residue between EtOAc and 2 N HCl aq
  6. washwashing the EtOAc layer with saturated NaHCO3 aq, brine
  7. dry with materialdrying over MgSO4
  8. filtrationThe solution was then filtered
  9. concentrationconcentrated
  10. customchromatographed on silica gel (1:4 EtOAc/hexanes)
  11. customthe product obtained
  12. customtriturated with CH2Cl2

Sources & evidence

ORD record
ord-33b1be52442d4f02a164479279c9d5d1
Source dataset
uspto-grants-2004_08
Patent number
US06774248B2

Reaction notes

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