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Potassium Phosphate, Tribasic → (S)-{1-[3-(4-pyridin-2-ylpiperazin-1-yl)phenyl]ethyl}carbamic acid tert-butyl ester

HRID 7591
Notes
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Reaction equation

HRID 7591 reaction equation
[C:1]([O:5][C:6](=[O:17])[NH:7][C@H:8]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12](Br)[CH:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2].[N:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.ClCCl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([O:5][C:6](=[O:17])[NH:7][C@H:8]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([N:27]2[CH2:28][CH2:29][N:24]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][N:18]=3)[CH2:25][CH2:26]2)[CH:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 944591-(2-Pyridyl)piperazineHCID 56971804(S)-N-Boc-1-(3-bromophenyl)ethylamine

Product 1

HCID 58680161(S)-{1-[3-(4-pyridin-2-ylpiperazin-1-yl)phenyl]ethyl}carbamic acid tert-butyl esterYield 64.2%

Reagents, catalysts & solvents 3

HCID 9811564
Bis(dibenzylideneacetone)palladium
Catalyst
HCID 6344DichloromethaneSolvent
HCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of (S)-[1-(3-bromophenyl)ethyl]carbamic acid tert-butyl ester (5.0 g, 16.7 mmol), 1-pyridin-2-ylpiperazine (10.9 g, 67 mmol), Pd2(dba)3 (1.55 g, 10 mol %), di-t-butyl-biphenylphosphine (0.51 g, 10 mol %), potassium phosphate (7.2 g, 34 mmol) in ethyleneglycol dimethyl ether (40 mL) was refluxed for 4 h. After cooling to room temperature, the reaction mixture was diluted with dichloromethane (100 mL) and the precipitate was filtered off. The filtrate was concentrated under vacuum. The crude product was purified by flash chromatography over silica with ethyl acetate/hexanes (1:2) to provide the title compounds as an oil (4.1 g, 64% yield).

Workup

  1. temperaturewas refluxed for 4 h
  2. filtrationthe precipitate was filtered off
  3. concentrationThe filtrate was concentrated under vacuum
  4. customThe crude product was purified by flash chromatography over silica with ethyl acetate/hexanes (1:2)

Sources & evidence

ORD record
ord-0a309e52be4b46568b3b57cb491326c7
Source dataset
uspto-grants-2006_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07087609B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes