Potassium Iodide → 4-(2-Methoxy-5-trifluoromethyl-phenyl)-piperazine

HRID 2185924Notes

Reaction equation

HRID 2185924 reaction equation
[CH3:1][O:2][C:3]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:4]=1[NH2:5].Cl.Cl[CH2:16][CH2:17][NH:18][CH2:19][CH2:20]Cl.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[OH-].[Na+]>C(O)CCC.O>[CH3:1][O:2][C:3]1[CH:9]=[CH:8][C:7]([C:10]([F:11])([F:12])[F:13])=[CH:6][C:4]=1[N:5]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1

Participants

8

Reactant 5

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 522769Bis(2-chloroethyl)amine hydrochlorideHCID 6006372-Methoxy-5-(trifluoromethyl)aniline

Product 1

HCID 151247944-(2-Methoxy-5-trifluoromethyl-phenyl)-piperazineYield 16%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 962WaterSolvent

Procedure

A mixture of 6.65 g of 2-methoxy-5-trifluoromethylaniline, 6.21 g of bis-(2-chloroethyl)amine hydrochloride, 4.71 g of anhydrous potassium carbonate and 0.34 g of anhydrous potassium iodide in 70 mL of n-butanol was refluxed for 50 hours. The solvent was removed at reduced pressure and the residue was taken up in 400 mL of diethyl ether. The suspension was acidified with 3N anhydrous hydrogen chloride in diethyl ether and stirred at room temperature for 3 hours. The solid was collected by filtration and dissolved in 50 mL of water. The solution was acidified with 36% hydrochloric acid, washed with 3×50 mL of diethyl ether, alkalinised with excess 36% sodium hydroxide and extracted with 2×70 mL of diethyl ether. The organic layer was dried over sodium sulphate and evaporated to dryness at reduced pressure to give a residue which was purified twice by flash chromatography, first using chloroform/3N methanolic ammonia 100:3 and subsequently using the upper layer of a 4:5:1 mixture of water, n-butanol and glacial acetic acid. The solvents were removed by evaporation in vacuo to give a residue which was dissolved in water. The mixture was alkalinised with 2N sodium hydroxide and extracted with chloroform; the organic layer was dried over sodium sulphate and the solvent was removed under reduced pressure to afford 1.42 g (16%) of Compound 17A as an oil.

Workup

  1. temperaturewas refluxed for 50 hours
  2. customThe solvent was removed at reduced pressure
  3. filtrationThe solid was collected by filtration
  4. dissolutiondissolved in 50 mL of water
  5. washwashed with 3×50 mL of diethyl ether
  6. extractionextracted with 2×70 mL of diethyl ether
  7. dry with materialThe organic layer was dried over sodium sulphate
  8. customevaporated to dryness at reduced pressure
  9. customto give a residue which
  10. customwas purified twice by flash chromatography, first using chloroform/3N methanolic ammonia 100:3
  11. additionthe upper layer of a 4:5:1 mixture of water, n-butanol and glacial acetic acid
  12. customThe solvents were removed by evaporation in vacuo
  13. customto give a residue which
  14. extractionextracted with chloroform
  15. dry with materialthe organic layer was dried over sodium sulphate
  16. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-dbf3122b191342e9b371a66511cbc5e6
Source dataset
uspto-grants-2002_06
Patent number
US06403594B1

Reaction notes

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