Dimethylformamide → 2-Fluoro-4-(5-fluoro-pyridin-2-ylmethoxy)benzaldehyde

HRID 1694032Notes

Reaction equation

HRID 1694032 reaction equation
CN(C)C=O.[F:6][C:7]1[CH:14]=[C:13]([OH:15])[CH:12]=[CH:11][C:8]=1[CH:9]=[O:10].[H-].[Na+].Cl[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][N:21]=1>O>[F:6][C:7]1[CH:14]=[C:13]([O:15][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][N:21]=2)[CH:12]=[CH:11][C:8]=1[CH:9]=[O:10]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 5872462-Fluoro-4-hydroxybenzaldehydeHCID 216980592-(Chloromethyl)-5-fluoropyridine

Product 1

HCID 592553562-Fluoro-4-(5-fluoro-pyridin-2-ylmethoxy)benzaldehydeYield 42.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To an N,N-dimethylformamide (20.0 mL) solution of 2-fluoro-4-hydroxy-benzaldehyde (1.48 g, 10.2 mmol) was added sodium hydride (411 mg, 10.3 mmol, 60% in oil) under nitrogen atmosphere at 0° C., which was stirred for 20 minutes at room temperature. 2-Chloromethyl-5-fluoro-pyridine (1.20 g, 8.56 mmol) described in Manufacturing Example 41-1-2 was then added at room temperature, and stirred for 30 minutes at 80° C. Water was added at room temperature to the reaction solution, which was then extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, and the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:heptane=1:5-1:2) to obtain the title compound (901 mg, 42.2%).

Workup

  1. additionwas then added at room temperature
  2. stirringstirred for 30 minutes at 80° C
  3. extractionwas then extracted with ethyl acetate
  4. washThe organic layer was washed with saturated aqueous sodium chloride
  5. customthe solvent was evaporated under a reduced pressure
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate:heptane=1:5-1:2)

Sources & evidence

ORD record
ord-7f030e0ff0a34a4a8d129877275bbda2
Source dataset
uspto-grants-2012_04
Patent number
US08158657B2

Reaction notes

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