1-bromo-4,4-dimethylpentan-2-one → HCID 178442241, compound

HRID 216374Notes

Reaction equation

HRID 216374 reaction equation
Br[CH2:2][C:3](=O)[CH2:4][C:5]([CH3:8])([CH3:7])[CH3:6].[F:10][C:11]([F:31])([C:15]([C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][N:25]=2)=[CH:20][CH:19]=1)([OH:17])[CH3:16])[C:12](=[NH:14])[NH2:13].C([O-])(=O)C.[Na+]>O1CCOCC1>[CH3:6][C:5]([CH3:8])([CH3:7])[CH2:4][C:3]1[N:13]=[C:12]([C:11]([F:31])([F:10])[C:15]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][N:25]=3)=[CH:20][CH:19]=2)([OH:17])[CH3:16])[NH:14][CH:2]=1

Participants

5

Reactant 3

HCID 2225851-bromo-4,4-dimethylpentan-2-oneHCID 517045Sodium AcetateHCID 686683062,2-Difluoro-3-[4-(5-fluoropyridin-2-yl)phenyl]-3-hydroxybutanimidamide

Product 1

HCID 178442241HCID 178442241, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

1-bromo-4,4-dimethylpentan-2-one (500 mg, 2.6 mmol) was added to an ambient temperature solution of 2,2-difluoro-3-[4-(5-fluoropyridin-2-yl)phenyl]-3-hydroxybutanimidamide (365 mg, 1.2 mmol) and sodium acetate (290 mg, 3.5 mmol) in 1,4-dioxane (20 mL). After stirring at reflux for 1 h, volatiles were removed in vacuo. The residue was partitioned between ethyl acetate and 1 N aqueous sodium hydroxide. The organic phase was washed with brine, dried (sodium sulfate) and concentrated in vacuo. Chromatography over silica eluting with 0-30% ethyl acetate/hexane afforded the title compound. 1H NMR (500 MHz, CDCl3) δ 8.50 (d, J=3.0 Hz, 1H), 7.83 (d, J=8.4 Hz, 2H), 7.67 (dd, J=4.3, 8.8 Hz, 1H), 7.58 (d, J=8.5 Hz, 2H), 7.45 (dt, J=2.8, 8.4, 1H) 6.69 (s, 1H), 2.39 (s, 2H), 1.77 (s, 3H), 0.84 (s, 9H).

Workup

  1. temperatureat reflux for 1 h
  2. customvolatiles were removed in vacuo
  3. customThe residue was partitioned between ethyl acetate and 1 N aqueous sodium hydroxide
  4. washThe organic phase was washed with brine
  5. dry with materialdried (sodium sulfate)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-332fa5d83da7490eb71dede5f920339c
Source dataset
uspto-grants-2012_06
Patent number
US08193228B2

Reaction notes

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