Triethylamine → 2-Chloro-4-[(4-fluorophenoxy)methyl]pyridine

HRID 15058

Reaction equation

HRID 15058 reaction equation
C(N(CC)CC)C.[Cl:8][C:9]1[CH:14]=[C:13]([CH2:15][OH:16])[CH:12]=[CH:11][N:10]=1.CS(Cl)(=O)=O.[F:22][C:23]1[CH:28]=[CH:27][C:26](O)=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.CN(C)C=O>[Cl:8][C:9]1[CH:14]=[C:13]([CH2:15][O:16][C:26]2[CH:27]=[CH:28][C:23]([F:22])=[CH:24][CH:25]=2)[CH:12]=[CH:11][N:10]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 97324-FluorophenolHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 7062237(2-Chloropyridin-4-yl)methanol

Product 1

HCID 622997992-Chloro-4-[(4-fluorophenoxy)methyl]pyridineYield 51%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Triethylamine (1.2 mL, 8.4 mmols) was added to a mixture of (2-chloro-4-pyridinyl)methanol (1.0 g, 7.0 mmols), methanesulfonyl chloride (0.6 mL, 7.7 mmols) and ethyl acetate (20 mL) under cooling with ice, and stirred at room temperature for 2 hours. Filtering the reaction liquid, the filtrate was concentrated. To the resulting residue, 4-fluorophenol (0.94 g, 8.4 mmols), potassium carbonate (1.93 g, 14.0 mmols) and N,N-dimethylformamide (20 mL) were added and s at 80° C. for 20 hours. Cooling the reaction liquid to room temperature, ethyl acetate was added thereto, followed by washing with saturated aqueous sodium hydrogencarbonate solution and saturated brine and drying over anhydrous sodium sulfate. Concentrating the solvent under reduced pressure, the residue was purified on silica gel column chromatography (KP-Sil, FLASH 40+M, chloroform) to provide the title compound (845 mg, 51%).

Workup

  1. temperatureunder cooling with ice
  2. filtrationFiltering
  3. customthe reaction liquid
  4. concentrationthe filtrate was concentrated
  5. waits at 80° C. for 20 hours
  6. temperatureCooling
  7. customthe reaction liquid to room temperature
  8. washby washing with saturated aqueous sodium hydrogencarbonate solution and saturated brine
  9. dry with materialdrying over anhydrous sodium sulfate
  10. concentrationConcentrating the solvent under reduced pressure
  11. customthe residue was purified on silica gel column chromatography (KP-Sil, FLASH 40+M, chloroform)

Sources & evidence

ORD record
ord-3208cf4fa1154931887786da26bad179
Source dataset
uspto-grants-2010_06
Patent number
US07732456B2

Linked notes

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