Toluene → 4-[(1-Benzylpiperidin-4-yl)(4-chlorophenylsulfonyl)methyl]pyridine

HRID 2080375Notes

Reaction equation

HRID 2080375 reaction equation
C1(C)C=CC=CC=1.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([CH2:18][C:19]2[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=2)(=[O:17])=[O:16])=[CH:11][CH:10]=1.C(C=P(CCCC)(CCCC)CCCC)#N.[CH2:41]([N:48]1[CH2:53][CH2:52][CH:51](O)[CH2:50][CH2:49]1)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>CO>[CH2:41]([N:48]1[CH2:53][CH2:52][CH:51]([CH:18]([S:15]([C:12]2[CH:13]=[CH:14][C:9]([Cl:8])=[CH:10][CH:11]=2)(=[O:17])=[O:16])[C:19]2[CH:20]=[CH:21][N:22]=[CH:23][CH:24]=2)[CH2:50][CH2:49]1)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 784611-Benzylpiperidin-4-olHCID 4622928Cyanomethylenetributylphosphorane2×HCID 230286434-(4-Chlorophenylsulfonylmethyl)pyridine

Product 1

HCID 231147574-[(1-Benzylpiperidin-4-yl)(4-chlorophenylsulfonyl)methyl]pyridineYield 35%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A toluene (5 ml) solution of the 4-(4-chlorophenylsulfonylmethyl)pyridine (70 mg, 0.261 mmol) obtained in Referential Example 2,1-benzylpiperidin-4-ol (103 mg, 0.538 mmol) and cyanomethylenetri-n-butylphosphorane (129 mg, 0.538 mol) was heated under reflux for 3 days under an argon atmosphere. After cooling to room temperature, 1-benzylpiperidin-4-ol (103 mg, 0.538 mmol) and cyanomethylenetri-n-butylphosphorane (129 mg, 0.538 mol) were added to the reaction mixture. Under an argon atmosphere, the resulting mixture was heated under reflux for 22 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue thus obtained was subjected to flash silica gel column chromatography. The fraction obtained from the methanol:methylene chloride (=1:10) eluate was concentrated under reduced pressure. The residue thus obtained was purified by high performance liquid chromatography (by using a mixed solvent system of water/acetonitrile/formic acid) to give the title compound (40 mg, 35%) as an amorphous substance.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 3 days under an argon atmosphere
  3. temperatureUnder an argon atmosphere, the resulting mixture was heated
  4. temperatureunder reflux for 22 hours
  5. temperatureAfter cooling to room temperature
  6. concentrationthe reaction mixture was concentrated under reduced pressure
  7. customThe residue thus obtained
  8. concentrationmethylene chloride (=1:10) eluate was concentrated under reduced pressure
  9. customThe residue thus obtained
  10. customwas purified by high performance liquid chromatography (

Sources & evidence

ORD record
ord-d306c5f6c4ec47158015cad93ad86c92
Source dataset
uspto-grants-2011_04
Patent number
US07932271B2

Reaction notes

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