Ammonium Chloride → HCID 86713636, compound

HRID 1430482Notes

Reaction equation

HRID 1430482 reaction equation
[F:1][C:2]1[CH:15]=[CH:14][C:13]([N+:16]([O-])=O)=[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-]>CCO.[Fe]>[F:1][C:2]1[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][C:3]=1[CH2:4][N:5]1[CH2:10][CH2:9][N:8]([CH3:11])[CH2:7][CH2:6]1

Participants

5

Reactant 2

HCID 25517Ammonium ChlorideHCID 86713635HCID 86713635, compound

Product 1

HCID 86713636HCID 86713636, compoundYield 75.1%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Conditions

Temperature
55 °C

Procedure

A solution of 1-(2-fluoro-5-nitrobenzyl)-4-methylpiperazine (0.577 g, 2.278 mmol) in EtOH (7 mL) was treated with satd. NH4Cl (4.75 mL, 22.78 mmol) followed by iron (powder) (1.272 g, 22.78 mmol) and the mixture heated at 55° C. overnight. The mixture was cooled to RT and gravity-filtered through filter paper, rinsing well with MeOH and DCM. The filtrate was concentrated to dryness. The residue was treated with EtOAc and water, then concentrated to dryness again. The resulting material was treated with THF (20 mL), sonicated for several hours and the solvent decanted from the solids. The solids were treated with additional THF (20 mL), sonicated again and the solvent decanted. The solids were treated with THF (20 mL) for a third time, stirred vigorously overnight, then the liquid was decanted. The combined decanted liquids were concentrated to dryness, treated with DCM, filtered to remove solids and concentrated to dryness to afford very hydroscopic 4-fluoro-3-((4-methylpiperazin-1-yl)methyl)aniline (382 mg, 75% yield). 1H NMR (400 MHz, DMSO-d6): δ 6.81 (m, 1H), 6.49 (m, 2H), 4.99 (s, 2H), 3.44 (s, 2H), 3.32 (s, 8H), 2.69 (s, 3H); MS (ESI) m/z: 224.2 [M+H]+.

Workup

  1. temperatureThe mixture was cooled to RT
  2. filtrationgravity-filtered
  3. filtrationthrough filter paper
  4. washrinsing well with MeOH and DCM
  5. concentrationThe filtrate was concentrated to dryness
  6. additionThe residue was treated with EtOAc and water
  7. concentrationconcentrated to dryness again
  8. additionThe resulting material was treated with THF (20 mL)
  9. customsonicated for several hours
  10. customthe solvent decanted from the solids
  11. additionThe solids were treated with additional THF (20 mL)
  12. customsonicated again
  13. customthe solvent decanted
  14. additionThe solids were treated with THF (20 mL) for a third time
  15. customthe liquid was decanted
  16. customThe combined decanted liquids
  17. concentrationwere concentrated to dryness
  18. additiontreated with DCM
  19. filtrationfiltered
  20. customto remove solids
  21. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-b1c4aa1ffa694cfd99dc27d8d1b326e5
Source dataset
uspto-grants-2015_01
Patent number
US08940756B2

Reaction notes

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