1-Ethylpiperazine → 1-{2,2-Dimethyl-3-[4-(4-methylphenyl)piperazin-1-yl]-3-oxopropyl}-4-ethylpiperazine

HRID 417992Notes

Reaction equation

HRID 417992 reaction equation
Br[CH:2]1[NH:7][CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[CH2:3]1.[CH3:15][C:16]([CH3:20])([CH3:19])[CH:17]=[O:18].[CH2:21]([N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1)[CH3:22]>CN1CCCC1=O.C(Cl)Cl>[CH3:15][C:16]([CH3:20])([C:17]([N:7]1[CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[CH2:3][CH2:2]1)=[O:18])[CH2:19][N:26]1[CH2:27][CH2:28][N:23]([CH2:21][CH3:22])[CH2:24][CH2:25]1

Participants

5

Reactant 2

HCID 791961-EthylpiperazineHCID 866357783-Bromo-1-(4-methylphenyl)piperazine 2,2-dimethylpropan-1-one

Product 1

HCID 579554721-{2,2-Dimethyl-3-[4-(4-methylphenyl)piperazin-1-yl]-3-oxopropyl}-4-ethylpiperazineYield 54%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
200 °C

Procedure

3-Bromo-1-(4-methylphenyl)piperazine-2,2-dimethylpropan-1-one (Example 37, step 1; 2.00 g, 5.92 mmol) was dissolved in N-methylpyrrolidinone (10 mL). N-Ethylpiperazine (1.50 mL, 11.8 mmol) was added. The reaction mixture was split into four batches and each was heated at 200° C. for 15 minutes in a Biotage Initiator microwave at high absorption. The reaction mixtures were combined and dissolved in DCM (300 mL), and washed with water (2×80 mL), brine (100 mL), dried (MgSO4) and then concentrated in vacuo. The residue was purified by reverse phase column chromatography (gradient eluting with MeOH in water, with 1% formic acid in each solvent, 0-30%). The resulting residue was dissolved in DCM (100 mL) and stirred with solid K2CO3 for 20 minutes, filtered and concentrated in vacuo, to give a colourless oil which was recrystallised from heptane to give 1-{2,2-dimethyl-3-[4-(4-methylphenyl)piperazin-1-yl]-3-oxopropyl}-4-ethylpiperazine (1.19 g, 48%) as a white solid.

Workup

  1. customThe reaction mixture was split into four batches
  2. customThe reaction mixtures
  3. washwashed with water (2×80 mL), brine (100 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by reverse phase column chromatography (gradient
  7. washeluting with MeOH in water, with 1% formic acid in each solvent, 0-30%)
  8. dissolutionThe resulting residue was dissolved in DCM (100 mL)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give a colourless oil which
  12. customwas recrystallised from heptane

Sources & evidence

ORD record
ord-bf54a8e033214d209d560f2ec829980c
Source dataset
uspto-grants-2012_01
Patent number
US08093248B2

Reaction notes

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