Sodium hydride → 2-[1-(3,5-dichlorobenzyl)-1H-imidazol-2-ylmethoxy]-6-fluoro-pyridine

HRID 2101520Notes

Reaction equation

HRID 2101520 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:13]=[C:14]([Cl:16])[CH:15]=1)[CH2:5][N:6]1[CH:10]=[CH:9][N:8]=[C:7]1[CH2:11][OH:12].[H-].[Na+].[F:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22](F)[N:21]=1.C(Cl)Cl.CO>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:13]=[C:14]([Cl:16])[CH:15]=1)[CH2:5][N:6]1[CH:10]=[CH:9][N:8]=[C:7]1[CH2:11][O:12][C:22]1[CH:23]=[CH:24][CH:25]=[C:20]([F:19])[N:21]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 739342,6-DifluoropyridineHCID 21226129Dichloromethane methanolHCID 57801498[1-(3,5-Dichloro-benzyl)-1H-imidazol-2-yl]-methanol

Product 1

HCID 578015012-[1-(3,5-dichlorobenzyl)-1H-imidazol-2-ylmethoxy]-6-fluoro-pyridineYield 66%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

[1-(3,5-Dichloro-benzyl)-1H-imidazol-2-yl]-methanol (300 mg, 1.17 mmol) was dissolved in DMF and NaH (46 mg, 1.17 mmol) was added under N2 atmosphere. After 20 minutes, 2,6-di-fluoropyridine (0.11 mL, 1.17 mmol) was added. The reaction mixture was stirred at room temperature for 1 h. The reaction was partitioned between EtOAc (50 mL) and water (50 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×75 mL). The combined organic extracts were washed with water (2×70 mL) and brine, dried over MgSO4, filtered and concentrated to yield a yellow solid. Chromatography (silica, 40:1 CH2Cl2/MeOH) afforded 2-[1-(3,5-dichlorobenzyl)-1H-imidazol-2-ylmethoxy]-6-fluoro-pyridine (270 mg, 66%).

Workup

  1. customThe reaction was partitioned between EtOAc (50 mL) and water (50 mL)
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc (2×75 mL)
  4. washThe combined organic extracts were washed with water (2×70 mL) and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a yellow solid

Sources & evidence

ORD record
ord-d23f5260bdd24d098820c7f8bddc4117
Source dataset
uspto-grants-2009_08
Patent number
US07572921B2

Reaction notes

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