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

HRID 584197Notes

Reaction equation

HRID 584197 reaction equation
[F:1][C:2]([F:37])([F:36])[C:3]1[CH:4]=[C:5]([CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:16]=[N:17][NH:18][CH:19]=2)[CH2:10][C@H:9]1[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[C:23]([CH3:28])[CH:22]=1)=[O:7].Br[CH2:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[F:35][C:32]([F:34])([F:33])[C:30]1[CH:29]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:36])[F:37])[CH:31]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:19]=[N:18][N:17]([CH2:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH:16]=2)[CH2:10][C@H:9]1[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[C:23]([CH3:28])[CH:22]=1)=[O:7]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 79177tert-Butyl bromoacetateHCID 54247854(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-(4-pyrazolylmethyl)piperazine

Product 1

HCID 86596439(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[[1-(tert-butoxycarbonylmethyl)-1H-pyrazol-4-yl]methyl]-2-(3,4-dimethylbenzyl)piperazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-(4-pyrazolylmethyl)piperazine (500 mg) and tert-butyl bromoacetate (225 mg) in N,N-dimethylformamide (7.5 ml) was added potassium carbonate (390 mg), and the mixture was stirred at 60° C. for 7 hours. Water was added to the mixture and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, evaporated under reduced pressure, and purified by column chromatography on a silica gel using a mixture of ethyl acetate and hexane (1:1) as eluent to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[[1-(tert-butoxycarbonylmethyl)-1H-pyrazol-4-yl]methyl]-2-(3,4-dimethylbenzyl)piperazine as an oil.

Workup

  1. extractionthe resulting mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. customevaporated under reduced pressure
  5. custompurified by column chromatography on a silica gel using
  6. additiona mixture of ethyl acetate and hexane (1:1) as eluent

Sources & evidence

ORD record
ord-b7ba6769c18c4e7d89c24694d31e255a
Source dataset
uspto-grants-2005_08
Patent number
US06924278B2

Reaction notes

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