4-Cyanophenol → 4-[1-(2-Isopropoxy-5-methanesulfonyl-benzoyl)-piperidin-4-yloxy]-benzonitrile

HRID 1711735Notes

Reaction equation

HRID 1711735 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1)#[N:2].[H-].[Na+].[CH:12]([O:15][C:16]1[CH:34]=[CH:33][C:32]([S:35]([CH3:38])(=[O:37])=[O:36])=[CH:31][C:17]=1[C:18]([N:20]1[CH2:25][CH2:24][CH:23](OS(C)(=O)=O)[CH2:22][CH2:21]1)=[O:19])([CH3:14])[CH3:13]>CN(C)C=O>[CH:12]([O:15][C:16]1[CH:34]=[CH:33][C:32]([S:35]([CH3:38])(=[O:37])=[O:36])=[CH:31][C:17]=1[C:18]([N:20]1[CH2:21][CH2:22][CH:23]([O:9][C:6]2[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)[CH2:24][CH2:25]1)=[O:19])([CH3:14])[CH3:13]

Participants

5

Reactant 3

HCID 130194-CyanophenolHCID 24758Sodium hydrideHCID 58673076Methanesulfonic acid 1-(2-isopropoxy-5-methanesulfonyl-benzoyl)-piperidin-4-yl ester

Product 1

HCID 586730634-[1-(2-Isopropoxy-5-methanesulfonyl-benzoyl)-piperidin-4-yloxy]-benzonitrileYield 21%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 0.14 mmol 4-cyanophenol in 1 ml N,N-dimethylformamide was added 0.19 mmol sodium hydride (60% suspension in oil) and the mixture was stirred at room temperature for 30 min. 0.12 mmol methanesulfonic acid 1-(2-isopropoxy-5-methanesulfonyl-benzoyl)-piperidin-4-yl ester was then added, and the reaction mixture was stirred at 60° C. for 2 h and then at 80° C. for 3 h. The reaction mixture was then cooled to room temperature and concentrated in vacuo. The crude material was purified by reversed phase HPLC (acetonitrile/water) to afford the title compound as a white crystalline solid (yield 21%). MS (m/e): 443.4 (M+H+, 100%).

Workup

  1. stirringthe reaction mixture was stirred at 60° C. for 2 h
  2. waitat 80° C. for 3 h
  3. temperatureThe reaction mixture was then cooled to room temperature
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by reversed phase HPLC (acetonitrile/water)

Sources & evidence

ORD record
ord-224b97be20cd40819c02f41767221df4
Source dataset
uspto-grants-2010_09
Patent number
US07790763B2

Reaction notes

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