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

HRID 2080376Notes

Reaction equation

HRID 2080376 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][CH:13]=[CH:12][N:11]=1.CN(C)C=O.[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([SH:29])=[CH:25][CH:24]=1.C(=O)([O-])[O-].[K+].[K+]>S(Cl)(Cl)=O.C(OCC)C>[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([S:29][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][CH:13]=[CH:12][N:11]=2)=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 7815p-ChlorothiophenolHCID 11430Potassium CarbonateHCID 23028683α-(2,5-Difluorophenyl)-2-pyridinemethanol

Product 1

HCID 231148862-{[(4-Chlorophenyl)sulfanyl](2,5-difluorophenyl)methyl}pyridineYield 92%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 24386Thionyl ChlorideSolvent

Procedure

The 2-[(2,5-difluorophenyl)-hydroxymethyl]pyridine (88 mg, 0.40 mmol) obtained in Referential Example 3 was dissolved in thionyl chloride (2.0 ml). To the resulting solution was added a catalytic amount of dimethylformamide, followed by stirring for 15 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added dioxane, and the resulting mixture was concentrated further. The residue was dissolved in dimethylformamide (5 ml). To the resulting solution were added 4-chlorobenzenethiol (79 mg, 0.55 mmol) and potassium carbonate (226 mg, 1.64 mmol) under a nitrogen atmosphere, and the 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 (128 mg, 92%) as an oil.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionTo the residue was added dioxane
  3. concentrationthe resulting mixture was concentrated further
  4. dissolutionThe residue was dissolved in dimethylformamide (5 ml)
  5. stirringthe 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-94c2df1bd7f3499d950d8bf29355d9e5
Source dataset
uspto-grants-2011_04
Patent number
US07932271B2

Reaction notes

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