Cesium carbonate → 4-[4-((S)-1-{tert-butoxycarbonyl-[2-(2-chloro-5-methoxy-4-nitro-phenyl)-ethyl]amino}-ethyl)phenyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1019775Notes

Reaction equation

HRID 1019775 reaction equation
[C:1]([O:5][C:6](=[O:31])[N:7]([C@H:22]([C:24]1[CH:29]=[CH:28][C:27](Br)=[CH:26][CH:25]=1)[CH3:23])[CH2:8][CH2:9][C:10]1[CH:15]=[C:14]([O:16][CH3:17])[C:13]([N+:18]([O-:20])=[O:19])=[CH:12][C:11]=1[Cl:21])([CH3:4])([CH3:3])[CH3:2].[C:32]([N:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1)([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.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:35]([O:34][C:32]([N:39]1[CH2:44][CH2:43][N:42]([C:27]2[CH:28]=[CH:29][C:24]([C@@H:22]([N:7]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:31])[CH2:8][CH2:9][C:10]3[CH:15]=[C:14]([O:16][CH3:17])[C:13]([N+:18]([O-:20])=[O:19])=[CH:12][C:11]=3[Cl:21])[CH3:23])=[CH:25][CH:26]=2)[CH2:41][CH2:40]1)=[O:33])([CH3:38])([CH3:36])[CH3:37]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 67469177[(S)-1-(4-Bromo-phenyl)-ethyl]-[2-(2-chloro-5-methoxy-4-nitro-phenyl)-ethyl]-carbamic acid tert-butyl ester

Product 1

HCID 674692684-[4-((S)-1-{tert-butoxycarbonyl-[2-(2-chloro-5-methoxy-4-nitro-phenyl)-ethyl]amino}-ethyl)phenyl]-piperazine-1-carboxylic acid tert-butyl esterYield 46%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of [(S)-1-(4-bromo-phenyl)-ethyl]-[2-(2-chloro-5-methoxy-4-nitro-phenyl)-ethyl]-carbamic acid tert-butyl ester (0.66 g, 1.17 mmol), N-Boc piperazine (0.44 g, 2.34 mmol), cesium carbonate (0.96 g, 2.92 mmol) and devphos (46.1 mg, 0.117 mmol) in 1,4-dioxane (5 mL) was degassed with argon. Pd2(dba)3 (0.054 g, 0.058 mmol) was added and the mixture heated to reflux for 3 hours under an argon atmosphere. The mixture was allowed to cool to room temperature, diluted with water (30 mL) and extracted with EtOAc (3×30 mL). The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using 20% EtOAc in hexane to give the title compound (0.33 g, 46%).

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 3 hours under an argon atmosphere
  3. extractionextracted with EtOAc (3×30 mL)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel using 20% EtOAc in hexane

Sources & evidence

ORD record
ord-5e83f03b42d0425da666f8f706dcda73
Source dataset
uspto-grants-2014_05
Patent number
US08716287B2

Reaction notes

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