Cesium carbonate → HCID 86728163, compound

HRID 627730Notes

Reaction equation

HRID 627730 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH3:10])[C:5](C#N)=[N:6][CH:7]=1.[C:11](=[O:14])([O-])[O-:12].[Cs+].[Cs+].FC(F)(F)S(O[CH2:23][C:24]([F:27])([F:26])[F:25])(=O)=O>CN(C=O)C.O.CCOC(C)=O>[CH3:10][C:4]1[C:5]([C:11]([OH:12])=[O:14])=[N:6][CH:7]=[C:2]([O:1][CH2:23][C:24]([F:27])([F:26])[F:25])[CH:3]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 299497345-Hydroxy-3-methylpyridine-2-carbonitrile

Product 1

HCID 86728163HCID 86728163, compoundYield 88.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-hydroxy-3-methylpicolinonitrile (0.487 g, 3.63 mmol) in DMF (5 mL) were added cesium carbonate (1.538 g, 4.72 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (1.011 ml, 4.36 mmol) and the resulting suspension was stirred at rt overnight. The reaction was diluted with water and EtOAc. The organic layer was washed with 1M LiCl solution and brine before drying over magnesium sulfate and concentrating under reduced pressure. The material was taken up in EtOH (20 mL) and NaOH, 1.0M aq (10.89 ml, 10.89 mmol) was added. The reaction was heated to 80° C. and stirred for 6 hours. The reaction was heated to reflux and stirred overnight. The reaction was continued at reflux for a total of 4 days. The reaction was cooled to rt and diluted with ether and water. The organic layer was washed with additional water and the combined aqueous layers were acidified to pH=1 (pH paper) by the addition of 1M HCl. The aqueous layer was extracted with DCM (2×) and the combined organics were brined, dried over magnesium sulfate and concentrated under reduced pressure to afford 3-methyl-5-(2,2,2-trifluoroethoxy)picolinic acid (0.754 g, 3.21 mmol, 88% yield). LC/MS (ESI+) m/z=236 (M+H).

Workup

  1. washThe organic layer was washed with 1M LiCl solution and brine
  2. dry with materialbefore drying over magnesium sulfate
  3. concentrationconcentrating under reduced pressure
  4. additionNaOH, 1.0M aq (10.89 ml, 10.89 mmol) was added
  5. temperatureThe reaction was heated to 80° C.
  6. stirringstirred for 6 hours
  7. temperatureThe reaction was heated
  8. temperatureto reflux
  9. stirringstirred overnight
  10. temperatureat reflux for a total of 4 days
  11. temperatureThe reaction was cooled to rt
  12. additiondiluted with ether and water
  13. washThe organic layer was washed with additional water
  14. additionthe combined aqueous layers were acidified to pH=1 (pH paper) by the addition of 1M HCl
  15. extractionThe aqueous layer was extracted with DCM (2×)
  16. dry with materialdried over magnesium sulfate
  17. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-fe084eea87944790be13e2924ff6e78b
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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