Dimethylformamide → 5-[[(4-Chlorophenyl)thio](2,5-difluorophenyl)methyl]-4-methyl-2-pyridinecarboxaldehyde

HRID 1641674Notes

Reaction equation

HRID 1641674 reaction equation
CCCCCC.C([Li])CCC.Br[C:13]1[CH:18]=[C:17]([CH3:19])[C:16]([CH:20]([S:29][C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=2)[C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=2[F:28])=[CH:15][N:14]=1.CN(C)[CH:39]=[O:40]>C1(C)C=CC=CC=1.C(OCC)(=O)C.O>[Cl:36][C:33]1[CH:34]=[CH:35][C:30]([S:29][CH:20]([C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=2[F:28])[C:16]2[C:17]([CH3:19])=[CH:18][C:13]([CH:39]=[O:40])=[N:14][CH:15]=2)=[CH:31][CH:32]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8058HexaneHCID 57736509HCID 57736509, compoundHCID 178418339Butyllithium

Product 1

HCID 577365055-[[(4-Chlorophenyl)thio](2,5-difluorophenyl)methyl]-4-methyl-2-pyridinecarboxaldehyde

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

In an argon atmosphere, a hexane solution of n-butyllithium (1.60 M, 2.52 ml, 4.03 mmol) was added to a solution of 2-bromo-5-[[(4-chlorophenyl)thio](2,5-difluorophenyl)methyl]-4-methylpyridine (1.48 g, 3.36 mmol) in toluene (40 ml) at −78° C. The reaction mixture was stirred for 1 hour, and then N,N-dimethylformamide (0.312 ml, 4.03 mmol) was added at the same temperature. After stirring the reaction mixture for 30 minutes, water was added thereto at the same temperature, and the mixture was allowed to warm to room temperature. Ethyl acetate was added to the reaction mixture, and the resulting mixture was washed with saturated aqueous ammonium chloride, and then with saturated brine. The organic layer was dried over anhydrous sodium sulfate and filtered, the filtrate was concentrated under reduced pressure, and the resulting residue was subjected to flash silica gel chromatography. The fraction obtained from an elution with hexane:ethyl acetate=10:1 was concentrated under reduced pressure, to obtain the title compound mg, 1.07 mmol, 32%) as a white solid.

Workup

  1. stirringAfter stirring the reaction mixture for 30 minutes
  2. washthe resulting mixture was washed with saturated aqueous ammonium chloride
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe fraction obtained from an elution with hexane
  7. concentrationethyl acetate=10:1 was concentrated under reduced pressure

Sources & evidence

ORD record
ord-fdefb9a310994567972fe6daa9efd190
Source dataset
uspto-grants-2012_02
Patent number
US08114886B2

Reaction notes

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