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

HRID 748823Notes

Reaction equation

HRID 748823 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.[S: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.C(OC(C)C)(C)C>[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][S:20][CH2:21][CH2:22]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 576296Tetrahydro-2H-thiopyran-4-olHCID 4622928Cyanomethylenetributylphosphorane2×HCID 99010282-(((4-Chlorophenyl)sulfonyl)methyl)-1,4-difluorobenzene

Product 1

HCID 231147914-[[(4-Chlorophenyl)sulfonyl](2,5-difluorophenyl)methyl]tetrahydrothiopyranYield 61%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 21881879Diisopropylether hexaneSolvent

Procedure

The 2-[(4-chlorophenyl)sulfonylmethyl]-1,4-difluorobenzene (500 mg, 1.65 mmol) obtained in Example 5 and tetrahydrothiopyran-4-ol (400 mg, 3.38 mmol) were dissolved in toluene (20 ml), followed by the addition of cyanomethylenetri-n-butylphosphorane (800 mg, 3.31 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 (400 mg, 1.66 mmol) was added. 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 subjected to flash silica gel chromatography, and the fraction obtained from the hexane:ethyl acetate=15:1 eluate was concentrated under reduced pressure to give a white solid. The white solid was washed with a hexane/diisopropyl ether mixture, whereby the title compound (404 mg, 1.00 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 resulting mixture was heated
  5. temperatureunder reflux for 14 hours
  6. temperatureto cool down
  7. customThe residue obtained
  8. concentrationby concentrating the reaction mixture under reduced pressure
  9. customthe fraction obtained from the hexane
  10. concentrationethyl acetate=15:1 eluate was concentrated under reduced pressure
  11. customto give a white solid

Sources & evidence

ORD record
ord-d8dbcc2001cd401dad37e19b416d8a5f
Source dataset
uspto-grants-2008_07
Patent number
US07399775B2

Reaction notes

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