Water → (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]methyl]piperazine

HRID 584189Notes

Reaction equation

HRID 584189 reaction equation
C(=O)([O-])[O-].[K+].[K+].Br[CH2:8][CH2:9][OH:10].[F:11][C:12]([F:47])([F:46])[C:13]1[CH:14]=[C:15]([CH:39]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:41]=1)[C:16]([N:18]1[CH2:23][CH2:22][N:21]([CH2:24][C:25]2[CH:26]=[N:27][NH:28][CH:29]=2)[CH2:20][C@H:19]1[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([CH3:37])=[C:33]([CH3:38])[CH:32]=1)=[O:17].O>CN(C)C=O>[F:45][C:42]([F:44])([F:43])[C:40]1[CH:39]=[C:15]([CH:14]=[C:13]([C:12]([F:11])([F:46])[F:47])[CH:41]=1)[C:16]([N:18]1[CH2:23][CH2:22][N:21]([CH2:24][C:25]2[CH:29]=[N:28][N:27]([CH2:8][CH2:9][OH:10])[CH:26]=2)[CH2:20][C@H:19]1[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([CH3:37])=[C:33]([CH3:38])[CH:32]=1)=[O:17]

Participants

6

Reactant 4

HCID 962WaterHCID 108982-BromoethanolHCID 11430Potassium CarbonateHCID 54247854(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-(4-pyrazolylmethyl)piperazine

Product 1

HCID 54495194(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]methyl]piperazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Potassium carbonate (158 mg) and 2-bromoethanol (0.045 ml) were added to a solution of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-(4-pyrazolylmethyl)piperazine (300 mg) in N,N-dimethylformamide (3 ml) at room temperature with stirring. After stirring at 100° C. for 5 hours, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and evaporated under reduced pressure. The obtained residue was purified by column chromatography (30 ml) on silica gel using a mixture of ethyl acetate and hexane (3:7) to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]methyl]piperazine (255.2 mg).

Workup

  1. stirringAfter stirring at 100° C. for 5 hours
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. customevaporated under reduced pressure
  6. customThe obtained residue was purified by column chromatography (30 ml) on silica gel using
  7. additiona mixture of ethyl acetate and hexane (3:7)

Sources & evidence

ORD record
ord-c24a3a8ed7404e7cb8ed45a46fab497a
Source dataset
uspto-grants-2005_08
Patent number
US06924278B2

Reaction notes

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