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

HRID 748732Notes

Reaction equation

HRID 748732 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:11][C:12]2[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH2:18]([N:25]1[CH2:30][CH2:29][CH:28](O)[CH2:27][CH2:26]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(C=P(CCCC)(CCCC)CCCC)#N>C1(C)C=CC=CC=1>[CH2:18]([N:25]1[CH2:30][CH2:29][CH:28]([CH:11]([S:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)(=[O:10])=[O:9])[C:12]2[CH:13]=[CH:14][N:15]=[CH:16][CH:17]=2)[CH2:27][CH2:26]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 784611-Benzylpiperidin-4-ol2×HCID 4622928Cyanomethylenetributylphosphorane2×HCID 230286434-(4-Chlorophenylsulfonylmethyl)pyridine

Product 1

HCID 231147574-[(1-Benzylpiperidin-4-yl)(4-chlorophenylsulfonyl)methyl]pyridine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A toluene (5 ml) solution of the 4-(4-chlorophenylsulfonylmethyl)pyridine (70 mg, 0.261 mmol) obtained in Example 119, 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, the reaction mixture was added with 1-benzylpiperidin-4-ol (103 mg, 0.538 mmol) and cyanomethylenetri-n-butylphosphorane (129 mg, 0.538 mol), followed by heating under reflux for 22 hours under an argon atmosphere. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was subjected to flash chromatography on a silica gel column. 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 (using a mixed solvent of water/acetonitrile/formic acid), whereby the title compound (40 mg, 35%) was obtained as an amorphous substance.

Workup

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

Sources & evidence

ORD record
ord-1adf79023dac494dbfed502ff7384f77
Source dataset
uspto-grants-2008_07
Patent number
US07399775B2

Reaction notes

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