Piperazine → 1-(3-Bromophenyl)-4-methylpiperazine

HRID 646475Notes

Reaction equation

HRID 646475 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[CH:3]=1.[CH3:9][N:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.C1CCN2C(=NCCC2)CC1.CC(C)([O-])C.[Na+].N1CCNCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[Br:8][C:4]1[CH:3]=[C:2]([N:13]2[CH2:14][CH2:15][N:10]([CH3:9])[CH2:11][CH2:12]2)[CH:7]=[CH:6][CH:5]=1

Participants

9

Reactant 5

HCID 4837PiperazineHCID 79271,3-DibromobenzeneHCID 531671-MethylpiperazineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 23676156Sodium t-butoxide

Product 1

HCID 534153291-(3-Bromophenyl)-4-methylpiperazineYield 78.4%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

1,3-Dibromobenzene (0.90 ml, 7.49 mmol), N-methylpiperazine (0.28 ml, 2.50 mmol) and anhydrous toluene (7 ml) were added by syringe to a dry, argon filled flask. The solution was thoroughly mixed before BINAP (47 mg) and Pd2 dba3 (23 mg) were delivered and the flask refilled with Argon and DBU (0.93 g, 2.5 equiv.) added via syringe. The reaction mixture was warmed to 60° C. before freshly ground sodium tertbutoxide was added in one portion to start the reaction. The reaction was left stirring at 60° C. overnight and the TLC analysis appeared to show that some piperazine was still present so the reaction was heated to 100° C. and stirred for another 24 hrs after which it was partitioned between EtOAc (20 ml) and water (20 ml). The aqueous layer was extracted again with EtOAc and the combined organics were washed with 1.6M HCl solution (2×10 ml). The acidic solution containing the product was then basified first with a similar volume of 1M NaOH solution to acid solution and then carefully solid sodium bicarbonate was added to make the pH=8.5 before extraction back into EtOAc (2×15 ml), which was washed with brine, dried over MgSO4 and evaporated to dryness to provide 0.50 g (78% yield) of the pure product as a yellow oil.

Workup

  1. additionadded via syringe
  2. additionwas added in one portion
  3. customthe reaction
  4. waitThe reaction was left
  5. temperaturewas heated to 100° C.
  6. stirringstirred for another 24 hrs after which it
  7. customwas partitioned between EtOAc (20 ml) and water (20 ml)
  8. extractionThe aqueous layer was extracted again with EtOAc
  9. washthe combined organics were washed with 1.6M HCl solution (2×10 ml)
  10. additionThe acidic solution containing the product
  11. additioncarefully solid sodium bicarbonate was added
  12. extractionbefore extraction back into EtOAc (2×15 ml), which
  13. washwas washed with brine
  14. dry with materialdried over MgSO4
  15. customevaporated to dryness

Sources & evidence

ORD record
ord-9d0e93bbb4954e3fa36950f43f8dbcce
Source dataset
uspto-grants-2010_04
Patent number
US07705027B2

Reaction notes

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