Potassium Carbonate → 1-(3,5-Difluorophenyl)piperazine

HRID 2284382Notes

Reaction equation

HRID 2284382 reaction equation
Cl.Cl[CH2:3][CH2:4][NH:5][CH2:6][CH2:7]Cl.[F:9][C:10]1[CH:11]=[C:12]([CH:14]=[C:15]([F:17])[CH:16]=1)[NH2:13].C(=O)([O-])[O-].[K+].[K+]>CCCCO>[F:9][C:10]1[CH:11]=[C:12]([N:13]2[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]2)[CH:14]=[C:15]([F:17])[CH:16]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 965953,5-DifluoroanilineHCID 522769Bis(2-chloroethyl)amine hydrochloride

Product 1

HCID 109872191-(3,5-Difluorophenyl)piperazine

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

Bis(2-chloroethyl)amine hydrochloride (2.07 g, 11.60 mmol) was added to a solution of 3,5-difluoroaniline (1.50 g, 11.62 mmol) in n-BuOH (20 mL). After the resulting solution was refluxed for 48 h, anhydrous potassium carbonate (1.61 g, 11.62 mmol) was added. After being refluxed for another 24 h, the reaction mixture was cooled, partitioned between water and CHCl3, and the aqueous layer was extracted with CHCl3. The combined organic layer was washed with water, dried over Na2SO4, and evaporated to dryness. Et2O and 1 N HCl/EtOH were added to the residue, and the precipitate was filtered to give TC-IV-174 (1.17 g, 30%) as a white solid.

Workup

  1. temperatureAfter the resulting solution was refluxed for 48 h
  2. temperatureAfter being refluxed for another 24 h
  3. temperaturethe reaction mixture was cooled
  4. custompartitioned between water and CHCl3
  5. extractionthe aqueous layer was extracted with CHCl3
  6. washThe combined organic layer was washed with water
  7. dry with materialdried over Na2SO4
  8. customevaporated to dryness
  9. additionEt2O and 1 N HCl/EtOH were added to the residue
  10. filtrationthe precipitate was filtered
  11. customto give TC-IV-174 (1.17 g, 30%) as a white solid

Sources & evidence

ORD record
ord-454108ae59de4b44b6df4ca04252d608
Source dataset
uspto-grants-2015_09
Patent number
US09145424B2

Reaction notes

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