Pyridine → 1-{2-(2-Fluoro-phenyl)-2-[hydroxyimino]-ethyl}-3-isopropenyl-1,3-dihydro-benzimidazol-2-one

HRID 1747354Notes

Reaction equation

HRID 1747354 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=O)[CH2:9][N:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]([C:19]([CH3:21])=[CH2:20])[C:11]1=[O:22].Cl.[NH2:25][OH:26].N1C=CC=CC=1>C(O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[N:25][OH:26])[CH2:9][N:10]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]([C:19]([CH3:21])=[CH2:20])[C:11]1=[O:22]

Participants

5

Reactant 3

HCID 1049PyridineHCID 443297Hydroxyamine hydrochlorideHCID 594974541-[2-(2-Fluoro-phenyl)-2-oxo-ethyl]-3-isopropenyl-1,3-dihydro-benzimidazol-2-one

Product 1

HCID 723080691-{2-(2-Fluoro-phenyl)-2-[hydroxyimino]-ethyl}-3-isopropenyl-1,3-dihydro-benzimidazol-2-oneYield 73.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 1-[2-(2-fluoro-phenyl)-2-oxo-ethyl]-3-isopropenyl-1,3-dihydro-benzimidazol-2-one (1.3 g, 4.2 mmol) in ethanol (50 ml) was added hydroxylamine hydrochloride (0.84 g, 12.2 mmol) followed by pyridine (1.7 ml, 21.0 mmol) at ambient temperature. The resulting mixture was warmed to 80° C. for 6 h, cooled to ambient temperature and concentrated. The remaining residue was diluted with water, 1M HCl and ethyl acetate. The layers were separated and the aqueous phase was extracted once more with ethyl acetate. The combined organics were dried (MgSO4), filtered and concentrated to give the crude product which was purified via column chromatography (silica gel, 50% EtOAc/hexanes). The product-containing fractions were combined and concentrated to give 1.0 g (73%) of the desired product as an oil which solidified on standing.

Workup

  1. temperaturecooled to ambient temperature
  2. concentrationconcentrated
  3. additionThe remaining residue was diluted with water, 1M HCl and ethyl acetate
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted once more with ethyl acetate
  6. dry with materialThe combined organics were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude product which
  10. customwas purified via column chromatography (silica gel, 50% EtOAc/hexanes)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-3d71513c1a2c4c63b6c17463a7c809b7
Source dataset
uspto-grants-2015_10
Patent number
US09150556B2

Reaction notes

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