Cesium carbonate → 1-(4,6-Dimethyl-pyridin-2-yl)-4-(2-methyl-4-nitro-phenyl)-piperazine

HRID 37862Notes

Reaction equation

HRID 37862 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][C:9]=1[CH3:17].[CH3:18][C:19]1[CH:24]=[C:23]([CH3:25])[N:22]=[C:21]([N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH:20]=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:18][C:19]1[CH:24]=[C:23]([CH3:25])[N:22]=[C:21]([N:26]2[CH2:27][CH2:28][N:29]([C:8]3[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][C:9]=3[CH3:17])[CH2:30][CH2:31]2)[CH:20]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 83315Benzene, 1-chloro-2-methyl-4-nitro-HCID 233680631-(4,6-Dimethylpyridin-2-YL)piperazine

Product 1

HCID 668515241-(4,6-Dimethyl-pyridin-2-yl)-4-(2-methyl-4-nitro-phenyl)-piperazineYield 27.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Procedure

Caesium carbonate (10.19 g, 31.38 mmol), 1-chloro-2-methyl-4-nitro-benzene (0.98 g, 5.75 mmol) and 1-(4,6-dimethyl-pyridin-2-yl)-piperazine (1.0 g, 5.23 mmol) were taken in toluene (35 mL) and degassed with argon for 15 min. A slurry of 2-dicyclophosphino-2′-(N,N-dimethylamino)-biphenyl (0.2 g, 0.52 mmol) and palladium acetate (0.116 g, 0.52 mmol) in toluene (5 mL) was added, the mixture degassed for another 10 min and then heated at reflux for 16 h. The mixture was cooled to room temperature and filtered, washing with ethyl acetate. The filtrate was washed with 2N hydrochloric acid, water, and brine, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to obtain the crude compound. Purification by column chromatography over silica gel (100-200 mesh) using 0-12% ethyl acetate in petroleum ether as eluent gave 1-(4,6-dimethyl-pyridin-2-yl)-4-(2-methyl-4-nitro-phenyl)-piperazine (0.463 g, 27%) as a solid.

Workup

  1. customdegassed with argon for 15 min
  2. customthe mixture degassed for another 10 min
  3. temperatureheated
  4. temperatureat reflux for 16 h
  5. filtrationfiltered
  6. washwashing with ethyl acetate
  7. washThe filtrate was washed with 2N hydrochloric acid, water, and brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum
  11. customto obtain the crude compound
  12. customPurification by column chromatography over silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-1dcc0993a9df45538c543723262d88fe
Source dataset
uspto-grants-2013_09
Patent number
US08524705B2

Reaction notes

Loading…