Potassium Carbonate → 5-(2,2,3,3-Tetrafluoro-propoxy)-pyridine-2-carboxylic acid methyl ester

HRID 571746Notes

Reaction equation

HRID 571746 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([O:10][CH3:11])=[O:9])=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].FC(F)(F)S(O[CH2:24][C:25]([F:30])([F:29])[CH:26]([F:28])[F:27])(=O)=O>CC(C)=O.CN(C=O)C.C(OCC)(=O)C.[NH4+].[Cl-]>[F:29][C:25]([F:30])([CH:26]([F:28])[F:27])[CH2:24][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([O:10][CH3:11])=[O:9])=[N:6][CH:7]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 37924752,2,3,3-Tetrafluoropropyl trifluoromethanesulfonateHCID 4715126Methyl 5-hydroxypyridine-2-carboxylate

Product 1

HCID 574758745-(2,2,3,3-Tetrafluoro-propoxy)-pyridine-2-carboxylic acid methyl esterYield 66.4%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

Methyl 5-hydroxypyridine-2-carboxylate (0.903 g, 5.90 mmol) is suspended in acetone (7 mL) and DMF (7 mL). 325 Mesh potassium carbonate (2.44 g, 17.69 mmol) is added in one portion and stirred at room temperature for 1.5 hours under nitrogen. 2,2,3,3-Tetrafluoropropyl trifluoromethanesulfonate (2.02 g, 7.67 mmol) is added drop wise and the mixture is stirred for 2 hours. The reaction mixture is diluted with ethyl acetate and saturated NH4Cl and extracted with ethyl acetate (3 times). The combined organic extracts are washed with brine, dried over Na2SO4, filtered, and the solvent removed in vacuo. The crude product is purified by silica gel flash chromatography, eluting with a gradient of 0-20% ethyl acetate in dichloromethane to give the title compound (1.047 g, 66%). ES/MS (m/e): 268.0 (M+1).

Workup

  1. stirringthe mixture is stirred for 2 hours
  2. extractionextracted with ethyl acetate (3 times)
  3. washThe combined organic extracts are washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customthe solvent removed in vacuo
  7. customThe crude product is purified by silica gel flash chromatography
  8. washeluting with a gradient of 0-20% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-e7b7d3f57c994e77bffbdf69ab6bebb9
Source dataset
uspto-grants-2015_05
Patent number
US09029367B2

Reaction notes

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