Water → 6-(Benzyloxy)nicotinaldehyde

HRID 640569Notes

Reaction equation

HRID 640569 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.CN(C)[CH:23]=[O:24].O>C(OCC)C.C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[N:10]=[CH:11][C:12]([CH:23]=[O:24])=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 111081912-Benzyloxy-5-bromopyridineHCID 178418339Butyllithium

Product 1

HCID 211022056-(Benzyloxy)nicotinaldehydeYield 86%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 2-benzyloxy-5-bromopyridine described in Manufacturing Example 231-1-1 (53.0 g, 201 mmol) in diethyl ether (500 mL) was added n-butyl lithium (82.8 mL, 2.67 M n-hexane solution, 221 mmol) was added dropwise on a dry ice-ethanol bath (−78° C.) under nitrogen atmosphere, which was stirred for 30 minutes at −78° C. While cooling at the same temperature, N,N-dimethylformamide (17.6 g, 241 mmol) was added to this reaction mixture, which was stirred for 30 minutes. Water and ethyl acetate were added to the reaction mixture, which was stirred for 10 minutes at room temperature, the organic layer was then separated. The organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was concentrated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:5 then 1:4) to obtain the title compound (36.8 g, 86%).

Workup

  1. additionwas added dropwise on a dry ice-ethanol bath (−78° C.) under nitrogen atmosphere
  2. additionwas added to this reaction mixture, which
  3. stirringwas stirred for 30 minutes
  4. stirringwas stirred for 10 minutes at room temperature
  5. customthe organic layer was then separated
  6. washThe organic layer was washed with water and saturated aqueous sodium chloride
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated under a reduced pressure
  10. customThe residue was purified by NH silica gel column chromatography (ethyl acetate

Sources & evidence

ORD record
ord-136db8a3b25e40179a57b1d53ad68d6a
Source dataset
uspto-grants-2010_04
Patent number
US07691882B2

Reaction notes

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