Potassium Iodide → (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[2-(2-hydroxyethoxy)ethyl]piperazine

HRID 584184Notes

Reaction equation

HRID 584184 reaction equation
[F:1][C:2]([F:31])([F:30])[C:3]1[CH:4]=[C:5]([CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:25]=1)[C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][C@H:9]1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([CH3:22])[CH:16]=1)=[O:7].Cl[CH2:33][CH2:34][O:35][CH2:36][CH2:37][OH:38].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C)C=O>[F:31][C:2]([F:1])([F:30])[C:3]1[CH:4]=[C:5]([CH:23]=[C:24]([C:26]([F:27])([F:28])[F:29])[CH:25]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:33][CH2:34][O:35][CH2:36][CH2:37][OH:38])[CH2:10][C@H:9]1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([CH3:22])[CH:16]=1)=[O:7]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 123612-(Chloroethoxy)ethanolHCID 54478438(2R)-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)piperazine

Product 1

HCID 86588510(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[2-(2-hydroxyethoxy)ethyl]piperazineYield 59.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)piperazine (500 mg), 2-(2-chloroethoxy)ethanol (168 mg), potassium carbonate (233 mg) and potassium iodide (56 mg) in N,N-dimethylformamide (2 ml) was heated with stirring at 50° C. for 17 hours, 60° C. for 13 hours and 70° C. for 1 hour. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine and dried over magnesium sulfate. After evaporation of the solvent, the resulting residue was purified by column chromatography on silica gel using dichloromethane-methanol (10:1) as eluent to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[2-(2-hydroxyethoxy)ethyl]piperazine (359 mg).

Workup

  1. temperaturewas heated
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. customAfter evaporation of the solvent
  6. customthe resulting residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-5f410e94e88649638e292d300f3e3fb6
Source dataset
uspto-grants-2005_08
Patent number
US06924278B2

Reaction notes

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