2-Bromoethanol → HCID 54206922, compound

HRID 1375007Notes

Reaction equation

HRID 1375007 reaction equation
[F:1][C:2]([F:43])([F:42])[C:3]1[CH:4]=[C:5]([CH:35]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:37]=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]([O:28][CH2:29][O:30][CH2:31][CH2:32][O:33][CH3:34])[CH:22]=1)=[O:7].Br[CH2:45][CH2:46][OH:47].C(=O)([O-])[O-].[K+].[K+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[F:43][C:2]([F:1])([F:42])[C:3]1[CH:4]=[C:5]([CH:35]=[C:36]([C:38]([F:39])([F:41])[F:40])[CH:37]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:19]=[N:18][N:17]([CH2:45][CH2:46][OH:47])[CH:16]=2)[CH2:10][C@H:9]1[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[C:23]([O:28][CH2:29][O:30][CH2:31][CH2:32][O:33][CH3:34])[CH:22]=1)=[O:7]

Participants

6

Reactant 3

HCID 108982-BromoethanolHCID 11430Potassium CarbonateHCID 86602696HCID 86602696, compound

Product 1

HCID 54206922HCID 54206922, compoundYield 68%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-[3-[(2-methoxyethoxy)methoxy]-4-methylbenzyl]-4-[(1H-pyrazol-4-yl)methyl]piperazine (254 mg), 2-bromoethanol (259 mg), potassium carbonate (228 mg) and tetrabutyl ammonium bromide (13 mg) in N,N-dimethylformamide (2.5 ml) was stirred at 100° C. for 2 days. After cooling, the mixture was evaporated in vacuo and water and ethyl acetate were added to the residue. The organic layer was separated, washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on alumina with a mixture of methylene chloride and methanol (100:1) as eluent to give (2R)-1-[3,5-bis(trifluoromethyl)-benzoyl]-2-[3-[(2-methoxyethoxy)methoxy]-4-methylbenzyl]-4-[[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]methyl]piperazine (185 mg).

Workup

  1. temperatureAfter cooling
  2. customthe mixture was evaporated in vacuo and water and ethyl acetate
  3. additionwere added to the residue
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over magnesium sulfate
  7. customevaporated in vacuo
  8. customThe residue was purified by column chromatography on alumina with a mixture of methylene chloride and methanol (100:1) as eluent

Sources & evidence

ORD record
ord-f8ef13bdfd854a79b4b2073fc7030e81
Source dataset
uspto-grants-2007_01
Patent number
US07166598B2

Reaction notes

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