Ammonium Chloride → 2-Fluoro-2-methyl-1-(pyridin-3-yl)propan-1-one

HRID 1747525Notes

Reaction equation

HRID 1747525 reaction equation
[CH3:1][CH:2]([CH3:11])[C:3]([C:5]1[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=1)=[O:4].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:32])(=O)=O)=CC=1.[Cl-].[NH4+]>C1COCC1.O>[F:32][C:2]([CH3:11])([CH3:1])[C:3]([C:5]1[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=1)=[O:4]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 588007N-FluorobenzenesulfonimideHCID 2733832Lithium HexamethyldisilazideHCID 122813372-Methyl-1-(pyridin-3-yl)propan-1-one

Product 1

HCID 674028752-Fluoro-2-methyl-1-(pyridin-3-yl)propan-1-oneYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-methyl-1-(pyridin-3-yl)propan-1-one (1.72 g, 11.5 mmol) obtained in Step 2 in THF (20 mL) was slowly added dropwise to lithium bis(trimethylsilyl)amide (1.0 mol/L solution in THF, 13.8 mL, 13.8 mmol) at −78° C. and the mixture was stirred at the same temperature for 30 minutes. Further, N-fluorobenzenesulfonimide (4.36 g, 13.8 mmol) was added and the mixture was stirred for 1.5 hours allowing the temperature to rise slowly to room temperature. A saturated aqueous ammonium chloride solution and water were added to the reaction mixture. Extraction with ethyl acetate, washing with saturated brine and drying over anhydrous sodium sulfate were performed. After filtration, the solvent in the filtrate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1) to give 2-fluoro-2-methyl-1-(pyridin-3-yl)propan-1-one (1.73 g, 89% yield).

Workup

  1. stirringthe mixture was stirred for 1.5 hours
  2. customto rise slowly to room temperature
  3. extractionExtraction with ethyl acetate
  4. washwashing with saturated brine
  5. dry with materialdrying over anhydrous sodium sulfate
  6. filtrationAfter filtration
  7. customthe solvent in the filtrate was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1)

Sources & evidence

ORD record
ord-9328ad3b920f4d6eb56fcff190581f3d
Source dataset
uspto-grants-2015_10
Patent number
US09150569B2

Reaction notes

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