p-Fluoronitrobenzene → 4-(4-Methylpiperazin-1-yl)aniline

HRID 1989001Notes

Reaction equation

HRID 1989001 reaction equation
C(=O)([O-])[O-].[K+].[K+].F[C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-])=O)=[CH:10][CH:9]=1.[CH3:17][N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1.[H][H]>CS(C)=O.CO.[Pd]>[CH3:17][N:18]1[CH2:23][CH2:22][N:21]([C:8]2[CH:13]=[CH:12][C:11]([NH2:14])=[CH:10][CH:9]=2)[CH2:20][CH2:19]1

Participants

8

Reactant 4

HCID 9590p-FluoronitrobenzeneHCID 11430Potassium CarbonateHCID 531671-MethylpiperazineHCID 178418361HCID 178418361, compound

Product 1

HCID 7372534-(4-Methylpiperazin-1-yl)anilineYield 95.7%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

Potassium carbonate (1.9 g, 14.2 mmol) was added to a mixture of 1-fluoro-4-nitrobenzene (1 g, 7.1 mmol) and 1-methyl-piperazine (0.94 mL, 8.5 mmol) in methyl sulfoxide (DMSO, 5 mL). The mixture was stirred at 80° C. for 3 hours. After cooling down, the residue was extracted into EtOAc. The organic layer was washed with water, brine and then dried with Na2SO4. Removal of the solvent in vacuo yielded an orange solid. The solid was dissolved in 25 mL of methanol and palladium on carbon (10% Pd/C, 50 mg) was added slowly. The system was sealed and blanketed with hydrogen. The mixture was stirred at rt for 16 hours under hydrogen. The catalyst was filtered through a celite pad and the solvent was evaporated to leave a dark purple solid (1.3 g, 80%). 1H NMR (300 MHz, CD3OD) δ (ppm): 6.90 (m, 2H), 6.81 (m, 2H), 3.38 (m, 4H), 3.26 (m, 4H), 2.93 (s, 3H).

Workup

  1. temperatureAfter cooling down
  2. extractionthe residue was extracted into EtOAc
  3. washThe organic layer was washed with water, brine
  4. dry with materialdried with Na2SO4
  5. customRemoval of the solvent in vacuo
  6. customyielded an orange solid
  7. customThe system was sealed
  8. stirringThe mixture was stirred at rt for 16 hours under hydrogen
  9. filtrationThe catalyst was filtered through a celite pad
  10. customthe solvent was evaporated

Sources & evidence

ORD record
ord-5538789a4c0b4481819fa9837497fc9a
Source dataset
uspto-grants-2010_01
Patent number
US07642270B2

Reaction notes

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