Acetic Acid → 3-Chloro-4-((4-methylpiperazin-1-yl)methyl)aniline

HRID 1622544Notes

Reaction equation

HRID 1622544 reaction equation
[Cl:1][C:2]1[CH:15]=[C:14]([N+:16]([O-])=O)[CH:13]=[CH:12][C:3]=1[CH2:4][N:5]1[CH2:10][CH2:9][N:8]([CH3:11])[CH2:7][CH2:6]1.[NH4+].[Cl-].C(O)(=O)C>CO.O.[Fe]>[Cl:1][C:2]1[CH:15]=[C:14]([CH:13]=[CH:12][C:3]=1[CH2:4][N:5]1[CH2:10][CH2:9][N:8]([CH3:11])[CH2:7][CH2:6]1)[NH2:16]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 25517Ammonium ChlorideHCID 667358141-(2-Chloro-4-nitrobenzyl)-4-methylpiperazine

Product 1

HCID 287219333-Chloro-4-((4-methylpiperazin-1-yl)methyl)anilineYield 61.4%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 22242641Methanol--water (1/1)Solvent

Procedure

To a solution of 1-(2-chloro-4-nitrobenzyl)-4-methylpiperazine (0.96 g, 3.6 mmol) in MeOH/water (4:1, 50 mL) was added 1.80 g (33.7 mmol) of NH4Cl and 1.47 g (26.3 mmol) of Fe dust and the mixture heated at reflux under an atmosphere of N2 for 2 h (HPLC indicated no progress). To this was added 4 mL of glacial acetic acid and the mixture heated at reflux for an additional 2 h. The reaction mixture was cooled to ambient temperature, filtered, and the filtrate concentrated. The residue was partitioned between EtOAc and saturated aq. NaHCO3, the separated aqueous layer was extracted with EtOAc, and the combined organics washed with brine and dried over Na2SO4. Upon concentration, the crude product was purified by silica gel chromatography (eluted with 5-7% MeOH/DCM; silica gel deactivated with 1% triethylamine/DCM) to provide 0.53 g of product.

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux under an atmosphere of N2 for 2 h (HPLC
  3. temperaturethe mixture heated
  4. temperatureat reflux for an additional 2 h
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated
  7. customThe residue was partitioned between EtOAc and saturated aq. NaHCO3
  8. extractionthe separated aqueous layer was extracted with EtOAc
  9. washthe combined organics washed with brine
  10. dry with materialdried over Na2SO4
  11. concentrationUpon concentration
  12. customthe crude product was purified by silica gel chromatography (eluted with 5-7% MeOH/DCM; silica gel deactivated with 1% triethylamine/DCM)

Sources & evidence

ORD record
ord-5e3e79498a4c4fdcb9e91d9ccc2d4b38
Source dataset
uspto-grants-2014_07
Patent number
US08778942B2

Reaction notes

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