Acetic Acid → 1-Boc-4-[2-(4-pyridinyl)ethyl]piperazine

HRID 496604Notes

Reaction equation

HRID 496604 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH:14]([C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1)=[CH2:15].C(O)(=O)C>C(O)C>[C:1]([N:8]1[CH2:9][CH2:10][N:11]([CH2:15][CH2:14][C:16]2[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=2)[CH2:12][CH2:13]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 75024-VinylpyridineHCID 143452tert-Butyl piperazine-1-carboxylate

Product 1

HCID 223216311-Boc-4-[2-(4-pyridinyl)ethyl]piperazineYield 88.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

1-Boc-piperazine (30 g, 285 mmol), 4-vinylpyridine (40 g, 216 mmol) and acetic acid (12.9 g, 215 mmol) were mixed in ethanol (400 mL) and heated to reflux for 18 h. The mixture was cooled to room temperature and concentrated under vacuum. The residue was dissolved in water and ethyl acetate and neutralized with satd NaHCO3. The layers were separated. The water layer was extracted with ethyl acetate. The organic layers were combined, washed with brine, dried (Na2SO4), filtered and concentrated. The crude product was purified by SiO2 chromatography to provide 1-Boc-4-[2-(4-pyridinyl)ethyl]piperazine (55.9 g, 87%) as an off white solid.

Workup

  1. temperatureheated
  2. temperatureto reflux for 18 h
  3. concentrationconcentrated under vacuum
  4. dissolutionThe residue was dissolved in water
  5. customThe layers were separated
  6. extractionThe water layer was extracted with ethyl acetate
  7. washwashed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product was purified by SiO2 chromatography

Sources & evidence

ORD record
ord-b194d5fe75a2401a832b02e649130178
Source dataset
uspto-grants-2005_09
Patent number
US06946467B2

Reaction notes

Loading…