Dimethylformamide → 5-(4-Methoxyphenyl)-4-methylnicotinaldehyde

HRID 2076678Notes

Reaction equation

HRID 2076678 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[N:9][CH:10]=[C:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[C:12]=1[CH3:13].CN(C)[CH:24]=[O:25].[Cl-].[NH4+]>O1CCCC1>[CH3:21][O:20][C:17]1[CH:18]=[CH:19][C:14]([C:11]2[CH:10]=[N:9][CH:8]=[C:7]([C:12]=2[CH3:13])[CH:24]=[O:25])=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 671193413-Bromo-5-(4-methoxyphenyl)-4-methylpyridineHCID 178418339Butyllithium

Product 1

HCID 862415675-(4-Methoxyphenyl)-4-methylnicotinaldehydeYield 44.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A n-butyllithium-1.58M n-hexane solution (3.9 ml, 6.13 mmol) was added dropwise to a solution of 3-bromo-5-(4-methoxyphenyl)-4-methylpyridine (1.55 g, 5.57 mmol) obtained in Example (76-1) in tetrahydrofuran (20 ml) at −78° C., and the mixture was stirred for 5 minutes. N,N-Dimethylformamide (0.87 ml, 11.2 mmol) was added dropwise thereto at the same temperature and the mixture was stirred for 30 minutes. A saturated aqueous ammonium chloride solution was added to the reaction mixture and the temperature of the mixture was raised to room temperature, and the mixture was extracted with ethyl acetate. The organic layer was successively washed with water and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by removing the solvent under reduced pressure was purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=4/1-2/3) to give 5-(4-methoxyphenyl)-4-methylnicotinaldehyde (0.56 g, yield: 44%).

Workup

  1. stirringat the same temperature and the mixture was stirred for 30 minutes
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was successively washed with water
  4. dry with materiala saturated aqueous NaCl solution and dried with anhydrous sodium sulfate
  5. customThe residue obtained
  6. customby removing the solvent under reduced pressure
  7. customwas purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=4/1-2/3)

Sources & evidence

ORD record
ord-ef7ed372401a4dc1bcd5217ade48f0e8
Source dataset
uspto-grants-2011_04
Patent number
US07923573B2

Reaction notes

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