Dimethylformamide → 2-{[(4-Chlorophenyl)sulfanyl](2,5-difluorophenyl)methyl}-5-methylpyridine

HRID 2080383Notes

Reaction equation

HRID 2080383 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9](O)[C:10]1[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][N:11]=1.CN(C)C=O.[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([SH:30])=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+]>S(Cl)(Cl)=O.C(OCC)C>[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([S:30][CH:9]([C:3]2[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=2[F:1])[C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][N:11]=2)=[CH:26][CH:25]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 7815p-ChlorothiophenolHCID 11430Potassium CarbonateHCID 23114839HCID 23114839, compound

Product 1

HCID 231146302-{[(4-Chlorophenyl)sulfanyl](2,5-difluorophenyl)methyl}-5-methylpyridineYield 66%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 24386Thionyl ChlorideSolvent

Procedure

The 2-[(2,5-difluorophenyl)-hydroxymethyl]-5-methylpyridine (125 mg, 0.53 mmol) obtained in Referential Example 5 was dissolved in thionyl chloride (1.0 ml). To the resulting solution was added a catalytic amount of dimethylformamide. The resulting mixture was stirred for 14 hours. The reaction mixture was concentrated under reduced pressure. Dioxane was added to the residue, followed by further concentration. The residue was dissolved in dimethylformamide (5 ml). To the resulting solution were added 4-chlorobenzenethiol (115 mg, 0.80 mmol) and potassium carbonate (438 mg, 3.18 mmol) under a nitrogen atmosphere. The resulting mixture was stirred at 50° C. for 1 hour. After the reaction mixture was cooled to room temperature, diethyl ether (50 ml) was added thereto. The resulting mixture was washed with water and brine. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (hexane:ethyl acetate=10:1) to give the title compound (120 mg, 66%) as an oil.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionDioxane was added to the residue
  3. concentrationfollowed by further concentration
  4. dissolutionThe residue was dissolved in dimethylformamide (5 ml)
  5. stirringThe resulting mixture was stirred at 50° C. for 1 hour
  6. washThe resulting mixture was washed with water and brine
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-92f0c8f0d19343b18d5aa80bdee68ab8
Source dataset
uspto-grants-2011_04
Patent number
US07932271B2

Reaction notes

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