Triethylamine → 3,3-Dimethyl-4-fluoro-1-(6-fluoro-pyridin-2-yl-oxy)-1-(1,2,4-triazol-1-yl)-butan-2-one

HRID 2295998Notes

Reaction equation

HRID 2295998 reaction equation
[CH3:1][C:2]([CH3:13])([CH2:11][F:12])[C:3](=[O:10])[CH2:4][N:5]1[CH:9]=[N:8][CH:7]=[N:6]1.C([O-])(=O)C.[Na+].BrBr.[F:21][C:22]1[N:27]=[C:26]([OH:28])[CH:25]=[CH:24][CH:23]=1.C(N(CC)CC)C>C(O)(=O)C.C(#N)C>[CH3:1][C:2]([CH3:13])([CH2:11][F:12])[C:3](=[O:10])[CH:4]([O:28][C:26]1[CH:25]=[CH:24][CH:23]=[C:22]([F:21])[N:27]=1)[N:5]1[CH:9]=[N:8][CH:7]=[N:6]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 24408BromineHCID 517045Sodium AcetateHCID 127695394-Fluoro-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)butan-2-oneHCID 178516046HCID 178516046, compound

Product 1

HCID 128067943,3-Dimethyl-4-fluoro-1-(6-fluoro-pyridin-2-yl-oxy)-1-(1,2,4-triazol-1-yl)-butan-2-oneYield 68%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6342AcetonitrileSolvent

Procedure

18.5 g (0.1 mole) of 3,3-dimethyl-4-fluoro-1-(1,2,4-triazol-1-yl)-butan-2-one were dissolved in 150 ml of glacial acetic acid, and, after adding 8.2 g (0.1 mole) of sodium acetate, 16 g (0.1 mole) of bromine were added dropwise at 45° C., until the mixture was completely decolorized. The mixture was then poured into ice-water and extracted with chloroform. The combined chloroform extracts were washed with sodium bicarbonate solution, dried over magnesium sulphate and concentrated. The oily 1-bromo-3,3-dimethyl-4-fluoro-1-(1,2,4-triazol-1-yl)-butan-2-one which remained was dissolved in 50 ml of acetonitrile, and 11.3 g (0.1 mole) of 6-fluoro-2-hydroxy-pyridine and 10.5 g (0.1 mole) of triethylamine, both dissolved in 120 ml of acetonitrile, were added, while stirring. The mixture was stirred under reflux for 1 hour. It was then concentrated by distilling off the solvent in vacuo, and the residue was stirred with water. The crystalline precipitate formed was filtered off and recrystallized from cyclohexane. 20 g (68% of theory) of 3,3-dimethyl-4-fluoro-1-(6-fluoro-pyridin-2-yl-oxy)-1-(1,2,4-triazol-1-yl)-butan-2-one of melting point 116° C. were obtained.

Workup

  1. additionwere added dropwise at 45° C., until the mixture
  2. extractionextracted with chloroform
  3. washThe combined chloroform extracts were washed with sodium bicarbonate solution
  4. dry with materialdried over magnesium sulphate
  5. concentrationconcentrated
  6. dissolutionThe oily 1-bromo-3,3-dimethyl-4-fluoro-1-(1,2,4-triazol-1-yl)-butan-2-one which remained was dissolved in 50 ml of acetonitrile
  7. additionwere added
  8. stirringThe mixture was stirred
  9. temperatureunder reflux for 1 hour
  10. concentrationIt was then concentrated
  11. distillationby distilling off the solvent in vacuo
  12. stirringthe residue was stirred with water
  13. customThe crystalline precipitate formed
  14. filtrationwas filtered off
  15. customrecrystallized from cyclohexane

Sources & evidence

ORD record
ord-59f5a935815c4a7695d5b884fbfe6e43
Source dataset
uspto-grants-1984_01
Patent number
US04427672

Reaction notes

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