p-Fluoronitrobenzene → 3,5-Dimethyl-1-(4-nitrophenyl)piperazine

HRID 1989046Notes

Reaction equation

HRID 1989046 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:17][CH:18]1[NH:23][CH:22]([CH3:24])[CH2:21][NH:20][CH2:19]1>CS(C)=O.O>[CH3:24][CH:22]1[NH:23][CH:18]([CH3:17])[CH2:19][N:20]([C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[CH2:21]1

Participants

6

Reactant 3

HCID 9590p-FluoronitrobenzeneHCID 11430Potassium CarbonateHCID 660562,6-Dimethylpiperazine

Product 1

HCID 28296203,5-Dimethyl-1-(4-nitrophenyl)piperazineYield 82.9%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 1-fluoro-4-nitrobenzene (2.12 mL, 20 mmol) and potassium carbonate (3.5 g, 25 mmol) in DMSO (10 mL) was added 3,5-dimethyl-piperazine (2.5 g, 22 mmol). The mixture was stirred at 100° C. for 2 hours. After cooing down, the mixture was diluted with water (50 mL) and extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine, dried with sodium sulfate (Na2SO4), and concentrated in vacuo to afford a yellow solid. Recrystallization from EtOAc/hexanes gave 3.9 g of 3,5-dimethyl-1-(4-nitro-phenyl)-piperazine, which was reduced via hydrogenation to give the title compound (purple solid, 3 g). 1H NMR (400 MHz, CDCl3) δ (ppm): 6.80 (d, J=8.8 Hz, 2H), 6.64 (d, J=8.8 Hz, 2H), 3.40 (br, 2H), 3.32 (d, J=9.5 Hz, 2H), 3.05 (m, 2H), 2.19 (t, J=10.5 Hz, 2H), 1.12 (s, 3H), 1.10 (s, 3H).

Workup

  1. extractionextracted with EtOAc (3×50 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried with sodium sulfate (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customto afford a yellow solid
  6. customRecrystallization from EtOAc/hexanes

Sources & evidence

ORD record
ord-661051dab9494fcdb79a7526664a7a44
Source dataset
uspto-grants-2010_01
Patent number
US07642270B2

Reaction notes

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