Tetrahydrofurfuryl alcohol → 2-[2-[(4-Chlorophenyl)sulfonyl]-2-(2,5-difluorophenyl)ethyl]tetrahydrofuran

HRID 748828Notes

Reaction equation

HRID 748828 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:11][C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=2[F:19])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH2:20](O)[CH:21]1[O:25][CH2:24][CH2:23][CH2:22]1.C(C=P(CCCC)(CCCC)CCCC)#N>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH:11]([C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=2[F:19])[CH2:20][CH:21]2[CH2:22][CH2:23][CH2:24][O:25]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 7360Tetrahydrofurfuryl alcoholHCID 4622928CyanomethylenetributylphosphoraneHCID 99010282-(((4-Chlorophenyl)sulfonyl)methyl)-1,4-difluorobenzene

Product 1

HCID 597508622-[2-[(4-Chlorophenyl)sulfonyl]-2-(2,5-difluorophenyl)ethyl]tetrahydrofuran

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

The 2-[(4-chlorophenyl)sulfonylmethyl]-1,4-difluorobenzene (200 mg, 0.661 mmol) obtained in Example 5 and tetrahydrofurfuryl alcohol (0.13 ml, 1.34 mmol) were dissolved in toluene (3 ml), followed by the addition of cyanomethylenetri-n-butylphosphorane (0.320 ml). Under an argon atmosphere, the resulting mixture was heated under reflux for 14 hours. The reaction mixture was then allowed to cool down. The residue obtained by concentrating the reaction mixture under reduced pressure was separated and purified by flash silica gel chromatography (using a hexane/ethyl acetate mixed solvent) to give a white solid. The white solid was washed with hexane, whereby obtained were the title Isomer 294-A (low polarity) (102 mg, 0.264 mmol, 40%) and the title Isomer 294-B (high polarity) (39 mg, 0.10 mmol, 15%), each as a white powder.

Workup

  1. temperatureUnder an argon atmosphere, the resulting mixture was heated
  2. temperatureunder reflux for 14 hours
  3. temperatureto cool down
  4. customThe residue obtained
  5. concentrationby concentrating the reaction mixture under reduced pressure
  6. customwas separated
  7. custompurified by flash silica gel chromatography (
  8. customto give a white solid
  9. washThe white solid was washed with hexane, whereby
  10. customobtained

Sources & evidence

ORD record
ord-9dcde044e5f340cd943ee0819b6fb605
Source dataset
uspto-grants-2008_07
Patent number
US07399775B2

Reaction notes

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