Sodium Hydroxide → 1-(2,5-Difluorophenyl)piperazine hydrochloride

HRID 639457Notes

Reaction equation

HRID 639457 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:3]=1[NH2:4].Cl.[Cl:11][CH2:12][CH2:13][NH:14][CH2:15][CH2:16]Cl.[OH-].[Na+]>C1(C)C(C)=CC=CC=1.CN1C(=O)CCC1>[ClH:11].[F:1][C:2]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:3]=1[N:4]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 677752,5-DifluoroanilineHCID 522769Bis(2-chloroethyl)amine hydrochloride

Product 1

HCID 185452801-(2,5-Difluorophenyl)piperazine hydrochloride

Reagents, catalysts & solvents 2

HCID 7237O-XyleneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

0.03 Mol of 2,5-difluoroaniline and 0.03 mol of bis-(2-chloroethyl)amine hydrochloride are suspended in 50 mL of xylene and 15 mL of NMP. The mixture is heated at 130° C. for 25 h while stirring, then cooled to RT and the solvents are evaporated. The residue is dissolved in water and 1 equivalent of 2N aqueous sodium hydroxide (NaOH) is added. The mixture is extracted with dichloromethane (DCM), and the organic layer is dried over anhydrous MgSO4, filtered and evaporated to dryness in vacuo. The residue is dissolved in acetone and 1 equivalent of HCL in diethyl ether (Et2O) is added. The precipitated product is collected by filtration and recrystallized from isopropanol to afford 1-(2,5-difluorophenyl)piperazine hydrochloride: m.p. 195° C. LC/MS (M+1=199.1). 1H NMR (DMSO-d6, 400 MHz) δ 3.22 (m, 4H), 3.28 (m, 4H), 6.83 (m, 1H), 6.97 (m, 1H), 7.22 (m, 1H), 9.46 (br s, NH).

Workup

  1. temperaturecooled to RT
  2. customthe solvents are evaporated
  3. dissolutionThe residue is dissolved in water
  4. extractionThe mixture is extracted with dichloromethane (DCM)
  5. dry with materialthe organic layer is dried over anhydrous MgSO4
  6. filtrationfiltered
  7. customevaporated to dryness in vacuo
  8. dissolutionThe residue is dissolved in acetone
  9. addition1 equivalent of HCL in diethyl ether (Et2O) is added
  10. filtrationThe precipitated product is collected by filtration
  11. customrecrystallized from isopropanol

Sources & evidence

ORD record
ord-b2ffd2bc036247a8ad34bb37cf9037ad
Source dataset
uspto-grants-2010_04
Patent number
US07691869B2

Reaction notes

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