2-Fluoropyridine → 2-{1-Methyl-2-[4-(3,5-difluorophenoxy)phenoxy]ethoxy}pyridine

HRID 1638296Notes

Reaction equation

HRID 1638296 reaction equation
[H-].[Na+].[CH3:3][CH:4]([OH:22])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][C:14]2[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[CH:15]=2)=[CH:9][CH:8]=1.[H][H].F[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1>CN(C)C=O.O>[CH3:3][CH:4]([O:22][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1)[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][C:14]2[CH:15]=[C:16]([F:21])[CH:17]=[C:18]([F:20])[CH:19]=2)=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 97462-FluoropyridineHCID 24758Sodium hydrideHCID 134559131-Methyl-2-[4-(3,5-difluorophenoxy)phenoxy]ethanolHCID 178418361HCID 178418361, compound

Product 1

HCID 133867412-{1-Methyl-2-[4-(3,5-difluorophenoxy)phenoxy]ethoxy}pyridineYield 72.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of sodium hydride (20 mg, 0.5 mmol; 60% in oil) in dimethylformamide (1 ml), a solution of 1-methyl-2-[4-(3,5-difluorophenoxy)phenoxy]ethanol (140 mg, 0.5 mmol) in dimethylformamide (1 ml) was dropwise added with stirring, and stirring was continued at room temperature until the generation of hydrogen gas ceased. 2-Fluoropyridine (97 mg, 1.0 mmol) was dropwise added thereto, and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water (40 ml) and extracted with toluene (20 ml) three times. The toluene layer was dried over anhydrous magnesium sulfate, and the solvent was removed by evaporation. The residue was purified by silica gel column chromatography to give 2-{1-methyl-2-[4-(3,5-difluorophenoxy)phenoxy]ethoxy}pyridine (129 mg) as pale yellow liquid. nD19.0 1.5602.

Workup

  1. stirringstirring
  2. stirringthe mixture was stirred at room temperature overnight
  3. extractionextracted with toluene (20 ml) three times
  4. dry with materialThe toluene layer was dried over anhydrous magnesium sulfate
  5. customthe solvent was removed by evaporation
  6. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-60471c40b19e4cdea8ebf8b188dc3dfe
Source dataset
uspto-grants-1989_11
Patent number
US04879292

Reaction notes

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