Cesium carbonate → Methyl 5-(difluoromethoxy)picolinate

HRID 627731Notes

Reaction equation

HRID 627731 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][N:6]=1)=[O:4].Cl[C:13]([F:18])([F:17])C([O-])=O.[Na+].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[F:17][CH:13]([F:18])[O:11][C:8]1[CH:9]=[CH:10][C:5]([C:3]([O:2][CH3:1])=[O:4])=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2734985Sodium chlorodifluoroacetateHCID 4715126Methyl 5-hydroxypyridine-2-carboxylate

Product 1

HCID 57827732Methyl 5-(difluoromethoxy)picolinateYield 74.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a RBF were added 5-hydroxy-2-pyridinecarboxylic acid methyl ester (1.2 ml, 9.94 mmol), sodium chlorodifluoroacetate (3.3 g, 21.54 mmol), and cesium carbonate (9.7 g, 29.8 mmol) in DMF (20 ml). The reaction mixture was heated to 100° C. for 3 h. Then it was cooled to RT. The reaction mixture was diluted with water and extracted with EtOAc. The organic extract was washed with water, brine and dried over MgSO4. It was filtered and concentrated. The crude product was purified by flash chromatography eluting with a gradient of 5% to 50% EtOAc in hexane, to provide methyl 5-(difluoromethoxy)picolinate (1.4962 g, 7.37 mmol, 74.1% yield). MS m/z: 204.3 [M+H].

Workup

  1. temperatureThen it was cooled to RT
  2. extractionextracted with EtOAc
  3. extractionThe organic extract
  4. washwas washed with water, brine
  5. dry with materialdried over MgSO4
  6. filtrationIt was filtered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography
  9. washeluting with a gradient of 5% to 50% EtOAc in hexane

Sources & evidence

ORD record
ord-75b6ec352526482cbc43e60567d2e627
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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