Triethylamine → 2-[(4-Chlorophenylthio)-(2,5-difluorophenyl)methyl]-5-(1,3-dioxolan-2-yl)pyridine

HRID 2080391Notes

Reaction equation

HRID 2080391 reaction equation
C(N(CC)CC)C.[CH3:8][S:9](Cl)(=O)=O.[F:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=1[CH:21](O)[C:22]1[CH:27]=[CH:26][C:25]([CH:28]2[O:32][CH2:31][CH2:30][O:29]2)=[CH:24][N:23]=1.C(=O)(O)[O-].[Na+].[Cl:39][C:40]1[CH:45]=[CH:44]C=[CH:42][C:41]=1S.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.CCOCC.C(Cl)Cl>[Cl:39][C:40]1[CH:45]=[CH:44][C:8]([S:9][CH:21]([C:15]2[CH:16]=[C:17]([F:20])[CH:18]=[CH:19][C:14]=2[F:13])[C:22]2[CH:27]=[CH:26][C:25]([CH:28]3[O:32][CH2:31][CH2:30][O:29]3)=[CH:24][N:23]=2)=[CH:42][CH:41]=1

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 80599o-ChlorothiophenolHCID 516892Sodium BicarbonateHCID 231146792-[(2,5-Difluorophenyl)-hydroxymethyl]-5-(1,3-dioxolan-2-yl)pyridine

Product 1

HCID 231146252-[(4-Chlorophenylthio)-(2,5-difluorophenyl)methyl]-5-(1,3-dioxolan-2-yl)pyridineYield 71.5%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Under a nitrogen atmosphere, triethylamine (1.08 ml, 7.8 mmol) and methanesulfonyl chloride (0.52 ml, 6.8 mmol) were added to a methylene chloride solution (30 ml) of the 2-[(2,5-difluorophenyl)-hydroxymethyl]-5-(1,3-dioxolan-2-yl)pyridine (1.52 g, 5.2 mmol) obtained in Referential Example 22 under ice cooling. The resulting mixture was stirred at room temperature for 3 hours. After addition of a saturated aqueous solution of sodium bicarbonate, the resulting mixture was extracted with ether. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue thus obtained was dissolved in dimethylformamide (30 ml). To the resulting solution were added chlorobenzenethiol (901 mg, 6.2 mmol) and potassium carbonate (1.08 g, 7.8 mmol), followed by stirring at 60° C. for 3 hours. After cooling to room temperature, the reaction mixture was diluted with ether. The diluted solution was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by silica gel chromatography (hexane:ethyl acetate=5:1) to give the title compound (1.56 g, 71%) as colorless needle crystals.

Workup

  1. customobtained in Referential Example 22 under ice cooling
  2. extractionthe resulting mixture was extracted with ether
  3. washThe extract was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue thus obtained
  7. stirringby stirring at 60° C. for 3 hours
  8. temperatureAfter cooling to room temperature
  9. washThe diluted solution was washed with water and brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe residue thus obtained
  13. customwas purified by silica gel chromatography (hexane:ethyl acetate=5:1)

Sources & evidence

ORD record
ord-667b9fcb1bd44444801be04b7bd2acb7
Source dataset
uspto-grants-2011_04
Patent number
US07932271B2

Reaction notes

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