2,3-Difluoropyridine → 1-(3-Fluoro-2-pyridyl)-3-methyl-pyrazole-4-carbaldehyde

HRID 1517567Notes

Reaction equation

HRID 1517567 reaction equation
C(O)(C)(C)C.[K].[CH3:7][C:8]1[C:12]([CH:13]=[O:14])=[CH:11][NH:10][N:9]=1.F[C:16]1[C:21]([F:22])=[CH:20][CH:19]=[CH:18][N:17]=1>CN(C)C=O.C(OCC)(=O)C>[F:22][C:21]1[C:16]([N:10]2[CH:11]=[C:12]([CH:13]=[O:14])[C:8]([CH3:7])=[N:9]2)=[N:17][CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 3

HCID 27831762,3-DifluoropyridineHCID 86639980Potassium tert-butoxideHCID 1784345503-methyl-1H-pyrazole-4-carbaldehyde

Product 1

HCID 582686081-(3-Fluoro-2-pyridyl)-3-methyl-pyrazole-4-carbaldehydeYield 42.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Potassium t-Butyl alcohol (29.25 g, 260.68 mmol) is added to a solution of 3-methyl-1H-pyrazole-4-carbaldehyde (26.00 g, 236.12 mmol) in dimethylformamide (250 mL) cooled with an aqueous bath. The mixture is stirred at room temperature for 10 min. Then, 2,3-difluoropyridine (25 g, 217.24 mmol) is added and the mixture is stirred at room temperature for 20 hr. The mixture is poured over an ice/water mixture and extracted in ethyl acetate (3×20 mL). Organics are dried over magnesium sulfate and solvent evaporated in vacuo. The residue is purified by silica gel chromatography using as eluent hexane/isopropyl alcohol to afford a crude material with residual dimethylformamide. The material is then dissolved in ethyl acetate (100 mL) and washed with water (3×20 mL). Aqueous phase is extracted with ethyl acetate (2×20 mL). Combined organics are dried over sodium sulfate and concentrated to give 19 g of the title compound. MS (m/z): 206 (M+1).

Workup

  1. temperaturecooled with an aqueous bath
  2. stirringthe mixture is stirred at room temperature for 20 hr
  3. extractionextracted in ethyl acetate (3×20 mL)
  4. dry with materialOrganics are dried over magnesium sulfate and solvent
  5. customevaporated in vacuo
  6. customThe residue is purified by silica gel chromatography
  7. customto afford a crude material with residual dimethylformamide
  8. washwashed with water (3×20 mL)
  9. extractionAqueous phase is extracted with ethyl acetate (2×20 mL)
  10. dry with materialCombined organics are dried over sodium sulfate
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-b60ed0c03e314df3bb39bb5e2808bcfd
Source dataset
uspto-grants-2012_07
Patent number
US08232289B2

Reaction notes

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