2-Bromopyridine → Ethyl difluoro(pyridin-2-yl)acetate

HRID 512022Notes

Reaction equation

HRID 512022 reaction equation
Br[C:2]([F:9])([F:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4].Br[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1.P([O-])(O)(O)=O.[K+]>CS(C)=O.C(OCC)(=O)C.[Cu]>[N:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[C:2]([F:9])([F:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4]

Participants

7

Reactant 3

HCID 79732-BromopyridineHCID 69585Ethyl bromodifluoroacetateHCID 516951Monobasic potassium phosphate

Product 1

HCID 10631894Ethyl difluoro(pyridin-2-yl)acetateYield 82%

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of ethyl bromodifluoroacetate (1.1 equiv.) and 2-bromopyridine (1 equiv.) in DMSO was added copper bronze (2.2 equiv.) and the mixture was heated to 50° C. with stirring for 2 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. A solution of potassium dihydrogen phosphate was added and the mixture stirred for 30 minutes before filtering. The copper salts were washed with ethyl acetate and the organic layer was washed with water. Solvent evaporation and purification by flash column chromatography on silica gel (diethyl ether-hexane) gave the title compound as a colorless oil in 82% yield.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringthe mixture stirred for 30 minutes
  3. filtrationbefore filtering
  4. washThe copper salts were washed with ethyl acetate
  5. washthe organic layer was washed with water
  6. customSolvent evaporation and purification by flash column chromatography on silica gel (diethyl ether-hexane)

Sources & evidence

ORD record
ord-d11e58cae3ee4c859c045630f53ec1f9
Source dataset
uspto-grants-2015_08
Patent number
US09102622B2

Reaction notes

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