Diethyl Ether → 3-{[(4-Chlorophenyl)sulfanyl](2,5-difluorophenyl)methyl}pyridine

HRID 2080381Notes

Reaction equation

HRID 2080381 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:11]=[N:12][CH:13]=[CH:14][CH:15]=1.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([SH:24])=[CH:20][CH:19]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)C>S(Cl)(Cl)=O.CN(C)C=O.C(OCC)(=O)C.CCCCCC>[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([S:24][CH:9]([C:3]2[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=2[F:1])[C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)=[CH:20][CH:19]=1

Participants

9

Reactant 4

HCID 3283Diethyl EtherHCID 7815p-ChlorothiophenolHCID 11430Potassium CarbonateHCID 12127979HCID 12127979, compound

Product 1

HCID 231145863-{[(4-Chlorophenyl)sulfanyl](2,5-difluorophenyl)methyl}pyridineYield 96.6%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 24386Thionyl ChlorideSolvent

Procedure

The 3-[(2,5-difluorophenyl)-hydroxymethyl]pyridine (87 mg, 0.39 mmol) obtained in Referential Example 11 was dissolved in thionyl chloride (1.0 ml). A catalytic amount of dimethylformamide was added to the resulting solution and the resulting mixture was stirred for 14 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added dioxane and the resulting mixture was concentrated further. The residue thus obtained was dissolved in dimethylformamide (5 ml), followed by the addition of 4-chlorobenzenethiol (84 mg, 0.58 mmol) and potassium carbonate (323 mg, 2.34 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 thus obtained was subjected to silica gel chromatography (hexane:ethyl acetate=1:1) to give the title compound (131 mg, 96%) 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. customThe residue thus obtained
  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
  9. customThe residue thus obtained

Sources & evidence

ORD record
ord-b9318c0b47064cc2935f9cc63113ee32
Source dataset
uspto-grants-2011_04
Patent number
US07932271B2

Reaction notes

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