Potassium Carbonate → p-Tolyl 4-(5-chloro-6-fluoropyridin-3-yloxy)-2,5-difluorobenzoate

HRID 2048080Notes

Reaction equation

HRID 2048080 reaction equation
C(=O)([O-])[O-].[K+].[K+].[F:7][C:8]1[CH:23]=[C:22](F)[C:21]([F:25])=[CH:20][C:9]=1[C:10]([O:12][C:13]1[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=1)=[O:11].[Cl:26][C:27]1[CH:28]=[C:29]([OH:34])[CH:30]=[N:31][C:32]=1[F:33]>CS(C)=O.CCOC(C)=O>[Cl:26][C:27]1[CH:28]=[C:29]([O:34][C:22]2[C:21]([F:25])=[CH:20][C:9]([C:10]([O:12][C:13]3[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=3)=[O:11])=[C:8]([F:7])[CH:23]=2)[CH:30]=[N:31][C:32]=1[F:33]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 224515553-Chloro-2-fluoro-5-hydroxypyridineHCID 580424084-Methylphenyl 2,4,5-trifluorobenzoate

Product 1

HCID 58042398p-Tolyl 4-(5-chloro-6-fluoropyridin-3-yloxy)-2,5-difluorobenzoateYield 56%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Potassium carbonate (1.40 g, 10.14 mmol) was added to a solution of 4-Methylphenyl 2,4,5-trifluorobenzoate (Preparation 12, 1.80 g, 6.76 mmol), 5-chloro-6-fluoropyridin-3-ol (1.05 g, 7.10 mmol) in DMSO and the mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted in EtOAc (50 mL), washed with water (2×25 mL) and the organic layer dried over sodium sulfate, filtered, and concentrated in vacuo. The remaining crude was then purified by silica gel chromatography eluting with 10 to 50% EtOAc in heptane to afford the title compound (1.48 g, 56%):

Workup

  1. washwashed with water (2×25 mL)
  2. dry with materialthe organic layer dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe remaining crude was then purified by silica gel chromatography
  6. washeluting with 10 to 50% EtOAc in heptane

Sources & evidence

ORD record
ord-7cec99d6b67a4b2b8fa8389d57b0cf6b
Source dataset
uspto-grants-2013_11
Patent number
US08592629B2

Reaction notes

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