Tetrahydrofuran → 1-(3-Methoxy-5-nitrophenyl)-4-methylpiperazine

HRID 869251Notes

Reaction equation

HRID 869251 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].C1COCC1.Br[C:13]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[C:15]([O:22][CH3:23])[CH:14]=1.[CH3:24][N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:23][O:22][C:15]1[CH:14]=[C:13]([N:28]2[CH2:29][CH2:30][N:25]([CH3:24])[CH2:26][CH2:27]2)[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=1

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 10796Cesium carbonateHCID 531671-MethylpiperazineHCID 122990761-Bromo-3-methoxy-5-nitrobenzene

Product 1

HCID 666427351-(3-Methoxy-5-nitrophenyl)-4-methylpiperazine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolvent

Procedure

After a mixture of palladium acetate (188 mg), 1,1′-binaphthalene-2,2′-diylbis(diphenylphosphine) (781 mg), cesium carbonate (4.09 g) and THF (20 mL) was stirred for 30 minutes, a mixture of 1-bromo-3-methoxy-5-nitrobenzene (1.94 g), 1-methylpiperazine (2.76 mL) and THF (20 mL) was added and heated under reflux for 14 hours. After cooling, the reaction liquid was diluted with ethyl acetate, and insoluble materials were separated by filtration. After extraction with 2M hydrochloric acid from the filtrate, the resulting aqueous layer was basified with 50% aqueous potassium hydroxide and then extracted with chloroform. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residue was purified by silica gel column chromatography (eluent; chloroform:methanol=100:0 to 20:1) to give 1-(3-methoxy-5-nitrophenyl)-4-methylpiperazine (1.01 g) as an orange syrup.

Workup

  1. additionwas added
  2. temperatureheated
  3. temperatureunder reflux for 14 hours
  4. temperatureAfter cooling
  5. customthe reaction liquid
  6. customwere separated by filtration
  7. extractionAfter extraction with 2M hydrochloric acid from the filtrate
  8. extractionextracted with chloroform
  9. dry with materialAfter the organic layer was dried over anhydrous magnesium sulfate
  10. distillationthe solvent was distilled off
  11. customthe residue was purified by silica gel column chromatography (eluent; chloroform:methanol=100:0 to 20:1)

Sources & evidence

ORD record
ord-982e74dcb9a34be284751fd209f893ce
Source dataset
uspto-grants-2015_03
Patent number
US08969336B2

Reaction notes

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