Tetrahydro-4H-pyran-4-ol → 4-[[(4-Chlorophenyl)sulfonyl](2,5-difluorophenyl)methyl]tetrahydropyran

HRID 748822Notes

Reaction equation

HRID 748822 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.[O:20]1[CH2:25][CH2:24][CH:23](O)[CH2:22][CH2:21]1.C(C=P(CCCC)(CCCC)CCCC)#N>C1(C)C=CC=CC=1.CCCCCC>[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])[CH:23]2[CH2:24][CH2:25][O:20][CH2:21][CH2:22]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 74956Tetrahydro-4H-pyran-4-olHCID 4622928Cyanomethylenetributylphosphorane2×HCID 99010282-(((4-Chlorophenyl)sulfonyl)methyl)-1,4-difluorobenzene

Product 1

HCID 231148714-[[(4-Chlorophenyl)sulfonyl](2,5-difluorophenyl)methyl]tetrahydropyranYield 61.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8058HexaneSolvent

Procedure

The 2-[(4-chlorophenyl)sulfonylmethyl]-1,4-difluorobenzene (200 mg, 0.661 mmol) obtained in Example 5 and tetrahydro-4H-pyran-4-ol (0.13 ml, 1.36 mmol) were dissolved in toluene (10 ml), followed by the addition of cyanomethylenetri-n-butylphosphorane (330 mg, 1.37 mmol). Under an argon atmosphere, the resulting mixture was heated under reflux for 14 hours. After the reaction mixture was allowed to cool down, cyanomethylenetri-n-butylphosphorane (200 mg, 0.829 mmol) was added thereto. Under an argon atmosphere, the mixture was heated under reflux for 14 hours. The reaction mixture was then allowed to cool down. The residue obtained by concentrating the mixture under reduced pressure was subjected to flash silica gel chromatography. The fraction obtained from the hexane:ethyl acetate=4:1 eluate was concentrated under reduced pressure to give a white solid. The white solid was washed with hexane, whereby the title compound (157 mg, 0.406 mmol, 61%) was obtained 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. temperatureUnder an argon atmosphere, the mixture was heated
  5. temperatureunder reflux for 14 hours
  6. temperatureto cool down
  7. customThe residue obtained
  8. concentrationby concentrating the mixture under reduced pressure
  9. customThe fraction obtained from the hexane
  10. concentrationethyl acetate=4:1 eluate was concentrated under reduced pressure
  11. customto give a white solid

Sources & evidence

ORD record
ord-43228b5e114c4ccf9011ede967e85e53
Source dataset
uspto-grants-2008_07
Patent number
US07399775B2

Reaction notes

Loading…