Benzyl Alcohol → 2-(Benzyloxy)-4-[(4-fluorophenoxy)methyl]pyridine

HRID 15059Notes

Reaction equation

HRID 15059 reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[CH:5]=[CH:4][N:3]=1.[CH2:17]([OH:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[H-].[Na+].O1CCCC1>C(OCC)(=O)C>[CH2:17]([O:24][C:2]1[CH:7]=[C:6]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[CH:5]=[CH:4][N:3]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 622997992-Chloro-4-[(4-fluorophenoxy)methyl]pyridine

Product 1

HCID 684318992-(Benzyloxy)-4-[(4-fluorophenoxy)methyl]pyridineYield 99.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-chloro-4-[(4-fluorophenoxy)methyl]pyridine (845 mg, 3.55 mmols), benzyl alcohol (0.48 mL, 4.62 mmols), sodium hydride (60% oiliness, 170 mg, 4.26 mmols) and tetrahydrofuran (20 mL) was refluxed for 16 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, hexane:ethyl acetate=10:0-17:3) to provide the title compound (1.09 g, 99%).

Workup

  1. temperaturewas refluxed for 16 hours
  2. temperatureCooling
  3. customthe reaction liquid to room temperature
  4. washby washing with saturated aqueous sodium hydrogencarbonate solution and saturated brine
  5. dry with materialdrying over anhydrous sodium sulfate
  6. concentrationConcentrating the solvent under reduced pressure
  7. customthe residue was purified on silica gel column chromatography (KP-Sil, FLASH 40+M, hexane:ethyl acetate=10:0-17:3)

Sources & evidence

ORD record
ord-cde868af8d5b4f72865aeb5332edbff1
Source dataset
uspto-grants-2010_06
Patent number
US07732456B2

Reaction notes

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