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

HRID 2080378Notes

Reaction equation

HRID 2080378 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]=[C:14]([CH3:16])[CH:13]=[CH:12][N:11]=1.[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([SH:25])=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)C>S(Cl)(Cl)=O.CN(C)C=O.C(OCC)(=O)C.CCCCCC>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([S:25][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]=[C:14]([CH3:16])[CH:13]=[CH:12][N:11]=2)=[CH:21][CH:20]=1

Participants

9

Reactant 4

HCID 3283Diethyl EtherHCID 7815p-ChlorothiophenolHCID 11430Potassium CarbonateHCID 23114779HCID 23114779, compound

Product 1

HCID 231146462-{[(4-Chlorophenyl)sulfanyl](2,5-difluorophenyl)methyl}-4-methylpyridineYield 151.2%

Reagents, catalysts & solvents 4

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

Procedure

After the 2-[(2,5-difluorophenyl)-hydroxymethyl]-4-methylpyridine (235 mg, 0.53 mmol) obtained in Referential Example 6 was dissolved in thionyl chloride (2.0 ml), a catalytic amount of dimethylformamide was added to the resulting solution. The resulting mixture was stirred for 16 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added dioxane, followed by further concentration. The residue thus obtained was dissolved in dimethylformamide (10 ml). To the resulting solution were added 4-chlorobenzenethiol (217 mg, 1.5 mmol) and potassium carbonate (828 mg, 6.0 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=10:1) to give the title compound (290 mg, 80%) as an oil.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionTo the residue was added dioxane
  3. concentrationfollowed by further concentration
  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-1e76e272006a48ecb1eb0b27a6b63d5c
Source dataset
uspto-grants-2011_04
Patent number
US07932271B2

Reaction notes

Loading…