Cesium carbonate → Methyl 5-(difluoromethoxy)picolinate

HRID 1842232Notes

Reaction equation

HRID 1842232 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:8]([F:18])([F:17])C(C1C=CC=CC=1)=O.[OH:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]([O:28][CH3:29])=[O:27])=[N:24][CH:25]=1.[Cl-].[NH4+]>CN(C=O)C.C(OCC)(=O)C>[F:17][CH:8]([F:18])[O:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]([O:28][CH3:29])=[O:27])=[N:24][CH:25]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 2382962-Chloro-2,2-difluoroacetophenoneHCID 4715126Methyl 5-hydroxypyridine-2-carboxylate

Product 1

HCID 57827732Methyl 5-(difluoromethoxy)picolinateYield 22.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Cesium carbonate (7.45 g) and 2-chloro-2,2-difluoroacetophenone (5.75 g) were added to a solution of methyl 5-hydroxypyridine-2-carboxylate (2.5 g) in DMF, and the mixture was stirred at 100° C. for three hours. The reaction solution was returned to room temperature. Aqueous ammonium chloride and ethyl acetate were added and the organic layer was separated. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. The organic layer was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (760 mg).

Workup

  1. customwas returned to room temperature
  2. customthe organic layer was separated
  3. washThe organic layer was washed with saturated aqueous sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationThe organic layer was concentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-6e5981d97b0d45f3869a21c6bd9588e9
Source dataset
uspto-grants-2015_02
Patent number
US08946210B2

Reaction notes

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