Potassium Iodide → 1-[5-Fluoro-2-(2,2,2-trifluoroethoxy)phenyl]piperazine

HRID 1840289Notes

Reaction equation

HRID 1840289 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:9][CH2:10][C:11]([F:14])([F:13])[F:12])=[C:6]([CH:8]=1)[NH2:7].Cl.Cl[CH2:17][CH2:18][NH:19][CH2:20][CH2:21]Cl.[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>C(O)CCC>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:9][CH2:10][C:11]([F:12])([F:13])[F:14])=[C:6]([N:7]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[CH:8]=1

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 522769Bis(2-chloroethyl)amine hydrochlorideHCID 174854135-Fluoro-2-(2,2,2-trifluoroethoxy)aniline

Product 1

HCID 234479041-[5-Fluoro-2-(2,2,2-trifluoroethoxy)phenyl]piperazineYield 14.5%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A stirred mixture of 0.52 g of Compound 5B, 0.45 g of bis-(2-chloroethyl)amine hydrochloride, 0.5 g of potassium iodide, 0.34 g of anhydrous potassium carbonate and 20 mL of n-butanol was refluxed for 32 hours under nitrogen. The solvent was removed under reduced pressure. The residue was treated with 10 mL of water and 10 mL of 20% aqueous sodium carbonate and extracted with 2×30 mL of ethyl acetate. The organic layer was washed with brine, dried over sodium sulphate and evaporated to dryness in vacuo. The residue was purified by flash chromatography (chloroform:2N ammonia in methanol gradient from 100:3 to 100:5) to afford 0.1 g (14%) of Compound 5C as an oil.

Workup

  1. temperaturewas refluxed for 32 hours under nitrogen
  2. customThe solvent was removed under reduced pressure
  3. additionThe residue was treated with 10 mL of water and 10 mL of 20% aqueous sodium carbonate
  4. extractionextracted with 2×30 mL of ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over sodium sulphate
  7. customevaporated to dryness in vacuo
  8. customThe residue was purified by flash chromatography (chloroform:2N ammonia in methanol gradient from 100:3 to 100:5)

Sources & evidence

ORD record
ord-0f8a78bd7dd34fb88bd05ffb06ded490
Source dataset
uspto-grants-2004_01
Patent number
US06680319B2

Reaction notes

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