Thionyl Chloride → 2,5-Dichloro-4-[(4-chlorophenylsulfonyl)(2,6-difluorophenyl)methyl]pyridine

HRID 2080533Notes

Reaction equation

HRID 2080533 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH:8]([C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[F:17])O)[C:5]([Cl:18])=[CH:4][N:3]=1.S(Cl)(Cl)=O.C(=O)(O)[O-].[Na+].[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([S:35]([O-:37])=[O:36])=[CH:31][CH:30]=1.[Na+]>ClCCl.CN(C)C=O.C(OCC)(=O)C.CCCCCC>[Cl:1][C:2]1[CH:7]=[C:6]([CH:8]([S:35]([C:32]2[CH:33]=[CH:34][C:29]([Cl:28])=[CH:30][CH:31]=2)(=[O:37])=[O:36])[C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[F:17])[C:5]([Cl:18])=[CH:4][N:3]=1

Participants

10

Reactant 4

HCID 24386Thionyl Chloride2×HCID 516892Sodium BicarbonateHCID 23114780(2,5-Dichloro-4-pyridyl)(2,6-difluorophenyl)methanolHCID 23664783Sodium 4-chlorobenzenesulfinate

Product 1

HCID 231146812,5-Dichloro-4-[(4-chlorophenylsulfonyl)(2,6-difluorophenyl)methyl]pyridineYield 66%

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

The (2,5-dichloro-4-pyridyl)(2,6-difluorophenyl)methanol (744 mg, 2.57 mmol) obtained in Referential Example 53 was suspended in dichloromethane (6 ml), followed by the addition of thionyl chloride (0.5 ml) and dimethylformamide (one drop). The resulting mixture was stirred at room temperature for 5 hours. To the reaction mixture was added thionyl chloride (1.0 ml) further. The resulting mixture was stirred at room temperature for 24 hours. The reaction mixture was concentrated. The residue thus obtained was neutralized with a saturated solution of sodium bicarbonate and then, extracted with dichloromethane. The extract was washed with water and brine, dried over magnesium sulfate and concentrated. The residue thus obtained was dissolved in dimethylformamide (10 ml). After the addition of sodium 4-chlorobenzenesulfinate (613 mg, 3.08 mmol), the resulting mixture was heated at 50° C. for 5 hours and then, 80° C. for 3 hours. The reaction mixture was diluted with ethyl acetate. The diluted solution was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue thus obtained was subjected to flash silica gel column chromatography. The fraction obtained from the hexane:ethyl acetate=4:1 eluate was concentrated. The resulting solid was recrystallized from diethyl ether-hexane to give the title compound (761 mg, 1.69 mmol, 66%) as a white solid.

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 24 hours
  2. concentrationThe reaction mixture was concentrated
  3. customThe residue thus obtained
  4. extractionextracted with dichloromethane
  5. washThe extract was washed with water and brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customThe residue thus obtained
  9. temperaturethe resulting mixture was heated at 50° C. for 5 hours
  10. wait80° C. for 3 hours
  11. washThe diluted solution was washed with water and brine
  12. dry with materialdried over magnesium sulfate
  13. concentrationconcentrated
  14. customThe residue thus obtained
  15. concentrationethyl acetate=4:1 eluate was concentrated
  16. customThe resulting solid was recrystallized from diethyl ether-hexane

Sources & evidence

ORD record
ord-e4d6619cdad246638b6f3a2a0447d451
Source dataset
uspto-grants-2011_04
Patent number
US07932271B2

Reaction notes

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