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o-Bromocumene → 1-(3-Benzyl-phenyl)-2-(S)-isopropyl-4-(2-isopropyl-phenyl)-piperazine

HRID 25861
Notes
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Reaction equation

HRID 25861 reaction equation
[CH2:1]([C:8]1[CH:9]=[C:10]([N:14]2[CH2:19][CH2:18][NH:17][CH2:16][C@@H:15]2[CH:20]([CH3:22])[CH3:21])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH:30]([CH3:32])[CH3:31].CC([O-])(C)C.[Na+].COCCOC.CCO>C1(C)C=CC=CC=1.CCOCC.C1(P(C2C=CC=CC=2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)C=CC=CC=1>[CH2:1]([C:8]1[CH:9]=[C:10]([N:14]2[CH2:19][CH2:18][N:17]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[CH:30]([CH3:32])[CH3:31])[CH2:16][C@@H:15]2[CH:20]([CH3:22])[CH3:21])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 23475o-BromocumeneHCID 20074477Dimethoxyethane ethanolHCID 207600044-(3'-Benzylphenyl)-3-(S)-isopropyl-piperazineHCID 23676156Sodium t-butoxide

Product 1

HCID 691295551-(3-Benzyl-phenyl)-2-(S)-isopropyl-4-(2-isopropyl-phenyl)-piperazineYield 62.2%

Reagents, catalysts & solvents 3

HCID 27349392'-(diphenylphosphanyl)-N,N-dimethyl-[1,1'-biphenyl]-2-amineCatalyst
HCID 1140TolueneSolvent
HCID 3283Diethyl EtherSolvent

Conditions

Temperature
80 °C

Procedure

110.7 mg (0.38 mmol) 4-(3′-Benzylphenyl)-3-(S)-isopropyl-piperazine (88a), 123.5 mg (0.62 mmol, 1.65 eq.) 1-Bromo-2-isopropyl-benzene 11.7 mg (12.7 μmol, 0.034 eq.) Pd2(dba)3, 7.4 mg (19.3 μmol, 0.05 eq.) 2-Diphenylphosphino-2′-dimethylamino-biphenyl and 87.3 mg (0.91 mmol, 2.42 eq.) NaOt-Bu were dissolved in 5 ml dry toluene. The resulting mixture was heated under N2 at 80° C. for 15.5 h. After cooling to room temperature the mixture was diluted with ether and washed with brine. The comb. org. fractions were dried over Na2SO4 and evaporated. Column chromatography (hexanes/EtOAc (9+1)) yielded 96.5 mg (0.23 mmol, 62.20%) 1-(3-Benzyl-phenyl)-2-(S)-isopropyl-4-(2-isopropyl-phenyl)-piperazine (89) as a clear oil.

Workup

  1. temperatureAfter cooling to room temperature the mixture
  2. washwashed with brine
  3. dry with materialfractions were dried over Na2SO4
  4. customevaporated

Sources & evidence

ORD record
ord-1b122892a0f943948cd06552bfdb562e
Source dataset
uspto-grants-2005_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06858600B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes