Sodium Iodide → 1-[2-(2,2,2-Trifluoroethoxy)phenyl]piperazine

HRID 2294108Notes

Reaction equation

HRID 2294108 reaction equation
[F:1][C:2]([F:13])([F:12])[CH2:3][O:4][C:5]1[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=1[NH2:7].Cl.Cl[CH2:16][CH2:17][NH:18][CH2:19][CH2:20]Cl.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>COCCOCCOC>[F:1][C:2]([F:12])([F:13])[CH2:3][O:4][C:5]1[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=1[N:7]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 522769Bis(2-chloroethyl)amine hydrochlorideHCID 27771172-(2,2,2-Trifluoroethoxy)aniline

Product 1

HCID 104915651-[2-(2,2,2-Trifluoroethoxy)phenyl]piperazineYield 52%

Reagents, catalysts & solvents 1

HCID 8150DiglymeSolvent

Procedure

A mixture of 2-(2,2,2-trifluoroethoxy)aniline (3.89 g, 20.4 mmol), bis(2-chloroethyl)amine hydrochloride (3.64 g, 20.4 mmol), potassium carbonate (2.82 g, 20.4 mmol) and sodium iodide (0.6 g, 4.1 mmol) in 10 mL of 2-methoxyethyl ether was heated at reflux for 4.5 hours. The mixture was cooled and 20 mL of an aqueous solution at pH 9 was added. The mixture was extracted with ethyl acetate (4×50 mL) and the combined organic layers were washed with brine, dried (Na2SO4) and concentrated. The residue was purified on silica gel by column chromatography eluting with 5% methanol/methylene chloride to give 1-[2-(2,2,2-trifluoroethoxy)phenyl]piperazine (2.74 g, 10.6 mmol). The free base was recrystallized from hydrochloric acid in alcohol to give 1-[2-(2,2,2-trifluoroethoxy)phenyl]piperazine hydrochloride, m.p. 172°-173° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4.5 hours
  3. temperatureThe mixture was cooled
  4. extractionThe mixture was extracted with ethyl acetate (4×50 mL)
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe residue was purified on silica gel by column chromatography
  9. washeluting with 5% methanol/methylene chloride

Sources & evidence

ORD record
ord-1a1483a7179f4be0b27ff25335d44782
Source dataset
uspto-grants-1997_11
Patent number
US05688795

Reaction notes

Loading…