Triethylamine → 5-Bromo-2-(4-fluoro-phenoxymethyl)-pyridine

HRID 1891709Notes

Reaction equation

HRID 1891709 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[H-].[Na+].Cl.[Br:12][C:13]1[CH:14]=[CH:15][C:16]([CH2:19]Cl)=[N:17][CH:18]=1.C(N(CC)CC)C>C(OCC)(=O)C.O.CN(C)C=O>[Br:12][C:13]1[CH:14]=[CH:15][C:16]([CH2:19][O:8][C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[N:17][CH:18]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 97324-FluorophenolHCID 24758Sodium hydrideHCID 534382005-Bromo-2-(chloromethyl)pyridine hydrochloride

Product 1

HCID 592552365-Bromo-2-(4-fluoro-phenoxymethyl)-pyridineYield 63.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To an N,N-dimethylformamide (40.0 mL) solution of 4-fluorophenol (3.00 g, 26.8 mmol) was added sodium hydride (1.00 g, 25.0 mmol, 60% in oil) on an ice bath (0° C.) under nitrogen atmosphere, which was stirred for 20 minutes at room temperature. To the reaction solution was then added a mixture of 5-bromo-2-chloromethyl-pyridine hydrochloride (4.6 g, 22.3 mmol) described in Manufacturing Example 54-1-2 and triethylamine (30.6 mL, 20.4 mmol), which was stirred for 10 minutes at room temperature. Water and ethyl acetate were added to the reaction mixture, and the organic layer was extracted with ethyl acetate. This organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The solvent was evaporated from the filtrate under a reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:heptane=1:4) to obtain the title compound (4.0 g, 63.6%).

Workup

  1. additionTo the reaction solution was then added
  2. stirringwas stirred for 10 minutes at room temperature
  3. extractionthe organic layer was extracted with ethyl acetate
  4. washThis organic layer was washed with water and saturated aqueous sodium chloride
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customThe solvent was evaporated from the filtrate under a reduced pressure
  8. customthe residue was purified by silica gel column chromatography (ethyl acetate:heptane=1:4)

Sources & evidence

ORD record
ord-317d0b8b57ea4c6295a593f928dfebb3
Source dataset
uspto-grants-2013_08
Patent number
US08507530B2

Reaction notes

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