Hydrochloric Acid → 1-((2,4-Difluorophenyl)methyl)piperazine dihydrochloride

HRID 2239786Notes

Reaction equation

HRID 2239786 reaction equation
[F:1][C:2]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[CH2:10][CH2:9][N:8](C(OC(C)(C)C)=O)[CH2:7][CH2:6]1.FC(F)(F)C(O)=O.[OH-].[Na+].[ClH:32]>C(Cl)Cl.C(Cl)Cl.CCOCC.CCOCC>[ClH:32].[ClH:32].[F:1][C:2]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[CH2:6][CH2:7][NH:8][CH2:9][CH2:10]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 684130721-BOC-4-(2,4-difluorobenzyl)piperazine

Product 1

HCID 669609111-((2,4-Difluorophenyl)methyl)piperazine dihydrochloride

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 21881112Ethyl ether methylene chlorideSolvent

Procedure

To a solution of 6.2 g (19.85 mmol) of the title A compound, t-butyl 4-(2,4-difluorobenzyl)piperazine-1-carboxylate in 50 mL of DCM at 0° C. is added 15 mL of trifluoroacetic acid. The reaction mixture is warmed to RT and stirred for 1 h, and 10 mL of 1 N aqueous sodium hydroxide (NaOH) are added. The mixture is extracted with 2×100 mL of DCM and the organic layer is washed with water, dried over anhydrous MgSO4 and evaporated to dryness in vacuo. The residue is dissolved in a mixture of DCM-Et2O and two equivalents of HCl in Et2O are added, the precipitate solid is collected by filtration and washed with acetone to afford 4-(2,4-difluorobenzyl)piperazine dihydrochloride as a white solid: m.p=237° C. LC/MS (M+1=213.1). 1H NMR (DMSO-d6, 400 MHz) δ 3.44 (m, 8H), 4.39 (s, 2H), 7.25 (dt, 1H, J=8.4 Hz and 1.6 Hz), 7.43 (dt, 1H, J=9.2 Hz and 2.0 Hz), 7.84 (dd, 1H, J=15.2 Hz and 8.4 Hz), 9.84 (br s, NH). Anal. calculated for (C11H14F2N2, 2HCl+0.25 H2O) C, 45.61; H, 5.74; Cl, 24.48; F, 13.12; N, 9.67; O, 1.38. Found C, 45.56; H, 5.90; N, 9.68.

Workup

  1. extractionThe mixture is extracted with 2×100 mL of DCM
  2. washthe organic layer is washed with water
  3. dry with materialdried over anhydrous MgSO4
  4. customevaporated to dryness in vacuo
  5. additionare added
  6. filtrationthe precipitate solid is collected by filtration
  7. washwashed with acetone

Sources & evidence

ORD record
ord-0a1026c7c1394bd8a6fa67cae82ee66b
Source dataset
uspto-grants-2010_05
Patent number
US07723343B2

Reaction notes

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