Water → 1-(3-Ethoxyphenyl)-piperazine dihydrochloride

HRID 1058955Notes

Reaction equation

HRID 1058955 reaction equation
Br[CH2:2][CH3:3].[OH:4][C:5]1[CH:6]=[C:7]([N:11]2[CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH2:12]2)[CH:8]=[CH:9][CH:10]=1.C(=O)([O-])[O-].[K+].[K+].O>CC(C)=O>[CH2:2]([O:4][C:5]1[CH:6]=[C:7]([N:11]2[CH2:12][CH2:13][NH:14][CH2:15][CH2:16]2)[CH:8]=[CH:9][CH:10]=1)[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 6332Ethyl BromideHCID 11430Potassium CarbonateHCID 18669061tert-Butyl 4-(3-hydroxyphenyl)piperazine-1-carboxylate

Product 1

HCID 145196341-(3-Ethoxyphenyl)-piperazine dihydrochlorideYield 46%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
0 °C

Procedure

Bromoethane (0.7 mL) was added to a mixture of 1,1-dimethylethyl 4-(3-hydroxyphenyl)-1-piperazinecarboxylate (Description 21, 500 mg, 1.8 mmol) and potassium carbonate (495 mg) in acetone (50 mL) and the mixture was heated under reflux for 13 h. The mixture was cooled, water (100 mL) was added and the mixture was extracted with ether (3×100 mL). The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with hexane/EtOAc (95:5). The residue was dissolved in dichloromethane (14 mL), cooled to 0° C. and trifluoroacetic acid (9 mL) was added. The mixture was stirred at 0° C. for 1 h., then allowed to warm to room temperature and saturated aqueous sodium bicarbonate solution (40 mL) was added. The mixture was extracted with dichloromethane, the combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure to give the title compound as a pale brown solid (210 mg, 46%). 1H NMR (250 MHz, CDCl3) δ1.43 (3H, t, J 7.6 Hz), 3.65-3.82 (8H, m), 3.98-4.13 (2H, m), 6.84-6.91 (2H, m), and 7.34-7.40 (1H, m).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 13 h
  3. temperatureThe mixture was cooled
  4. extractionthe mixture was extracted with ether (3×100 mL)
  5. dry with materialThe combined organic fractions were dried (MgSO4)
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel
  8. washeluting with hexane/EtOAc (95:5)
  9. dissolutionThe residue was dissolved in dichloromethane (14 mL)
  10. additiontrifluoroacetic acid (9 mL) was added
  11. temperatureto warm to room temperature
  12. additionsaturated aqueous sodium bicarbonate solution (40 mL) was added
  13. extractionThe mixture was extracted with dichloromethane
  14. dry with materialthe combined organic fractions were dried (MgSO4)
  15. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-259e4da6d4c54809b6763d465bfe6180
Source dataset
uspto-grants-2003_02
Patent number
US06518273B1

Reaction notes

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