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

HRID 342544Notes

Reaction equation

HRID 342544 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+].[OH-].[NH4+]>O.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

8

Reactant 5

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 14923Ammonium HydroxideHCID 522769Bis(2-chloroethyl)amine hydrochlorideHCID 27771172-(2,2,2-Trifluoroethoxy)aniline

Product 1

HCID 104915651-[2-(2,2,2-Trifluoroethoxy)phenyl]piperazineYield 75.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8150DiglymeSolvent

Procedure

A mixture of 2-(2,2,2-trifluoroethoxy)aniline (2.85 g, 14.9 mmol), bis(2-chloroethyl)amine hydrochloride (2.66 g, 14.9 mmol), potassium carbonate (2.06 g, 14.9 mmol), sodium iodide (0.45 g, 3 mmol) and bis(2-methoxyethyl) ether (7.3 mL) was heated 8 hours at reflux. The reaction mixture then was cooled, treated with concentrated ammonium hydroxide, poured into water (30 mL) and extracted with ethyl acetate (3×30 mL). The combined extracts were washed with water (2×30 mL) and brine (1×30 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with methylene chloride/methanol (95:5) to give 1-[2-(2,2,2-trifluoroethoxy)phenyl]piperazine (2.93 g, 11.2 mmol), m.p. 107°-108° C.

Workup

  1. temperaturewas heated 8 hours
  2. temperatureat reflux
  3. temperatureThe reaction mixture then was cooled
  4. extractionextracted with ethyl acetate (3×30 mL)
  5. washThe combined extracts were washed with water (2×30 mL) and brine (1×30 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography on silica gel eluting with methylene chloride/methanol (95:5)

Sources & evidence

ORD record
ord-be16ff5cfa99409ba94463ef980642cd
Source dataset
uspto-grants-1999_01
Patent number
US05859014

Reaction notes

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