Sodium hydride → Methyl 5-chloro-2-{[(5-fluoropyridin-3-yl)oxy]methyl}benzoate

HRID 493547Notes

Reaction equation

HRID 493547 reaction equation
[F:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([OH:8])[CH:7]=1.[H-].[Na+].Br[CH2:12][C:13]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:14]=1[C:15]([O:17][CH3:18])=[O:16]>CN(C)C=O>[Cl:23][C:20]1[CH:21]=[CH:22][C:13]([CH2:12][O:8][C:6]2[CH:5]=[N:4][CH:3]=[C:2]([F:1])[CH:7]=2)=[C:14]([CH:19]=1)[C:15]([O:17][CH3:18])=[O:16]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27629063-Fluoro-5-hydroxypyridineHCID 51358462Methyl 2-(bromomethyl)-5-chlorobenzoate

Product 1

HCID 68865859Methyl 5-chloro-2-{[(5-fluoropyridin-3-yl)oxy]methyl}benzoateYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 3-fluoro-5-hydroxypyridine (34 mg, 0.30 mmol) in dimethylformamide (3 mL) was added sodium hydride (60% dispersion in mineral oil, 12 mg, 0.30 mmol) at 0° C. and the mixture was stirred at room temperature for 15 minutes. To the mixture was added methyl 2-(bromomethyl)-5-chlorobenzoate (100 mg, 0.4 mmol) in dimethylformamide and the mixture was stirred at room temperature overnight. The mixture was quenched with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and evaporated. The residue was purified by flash column chromatography on silica gel to afford 47 mg (53%) of the title compound:

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. customThe mixture was quenched with water
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. customThe residue was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-c4ff2a4884064c348c899a574c089399
Source dataset
uspto-grants-2009_05
Patent number
US07534914B2

Reaction notes

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