Potassium Iodide → (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)-4-(2-phenyl-2-ethanon-1-yl)piperazine

HRID 10168

Reaction equation

HRID 10168 reaction equation
[CH2:1](Br)[C:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[O:3].[F:11][C:12]([F:42])([F:41])[C:13]1[CH:14]=[C:15]([CH:34]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:36]=1)[C:16]([N:18]1[CH2:23][CH2:22][NH:21][CH2:20][C@H:19]1[CH2:24][C:25]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[NH:27][CH:26]=1)=[O:17].[I-].[K+].C(N(C(C)C)CC)(C)C>C(#N)C>[F:40][C:37]([F:38])([F:39])[C:35]1[CH:34]=[C:15]([CH:14]=[C:13]([C:12]([F:11])([F:41])[F:42])[CH:36]=1)[C:16]([N:18]1[CH2:23][CH2:22][N:21]([CH2:1][C:2]([C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)=[O:3])[CH2:20][C@H:19]1[CH2:24][C:25]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[NH:27][CH:26]=1)=[O:17]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 6259Phenacyl bromideHCID 81531DiisopropylethylamineHCID 10972505(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)piperazine

Product 1

HCID 58681866(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)-4-(2-phenyl-2-ethanon-1-yl)piperazineYield 85.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of phenacyl bromide (0.88 g), (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)piperazine (2 g), potassium iodide (catalytical), diisopropyl-ethylamine (0.77 mL), and acetonitrile (20 mL) was stirred at room temperature overnight. After cooling to room temperature the solvent was removed in vacuo, and the residue treated with dichloromethane and NaOH (2N). The layers were separated, the organic layer was dried (Na2SO4), and concentrated in vacuo. The residue was purified by flash chromatography (SiO2, CH2Cl2/MeOH 97/3) to afford (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(1H-indol-3-ylmethyl)-4-(2-phenyl-2-ethanon-1-yl)piperazine 2.16 g (85%). MH+ 574, Rf 0.44 (CH2Cl2/MeOH 97/3).

Workup

  1. temperatureAfter cooling to room temperature the solvent
  2. customwas removed in vacuo
  3. additionthe residue treated with dichloromethane and NaOH (2N)
  4. customThe layers were separated
  5. dry with materialthe organic layer was dried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography (SiO2, CH2Cl2/MeOH 97/3)

Sources & evidence

ORD record
ord-432a32e32913427491b423a3888d4dd7
Source dataset
uspto-grants-2006_08
Patent number
US07094779B2

Linked notes

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