Potassium Carbonate → 4-(((2R)-1,4-dibenzyl-2-piperazinyl)methyl)-3,3-dimethyl-2-piperazinone

HRID 1972594Notes

Reaction equation

HRID 1972594 reaction equation
CS(O[CH2:6][C@H:7]1[CH2:12][N:11]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:10][CH2:9][N:8]1[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=O)=O.[CH3:27][C:28]1([CH3:35])[NH:33][CH2:32][CH2:31][NH:30][C:29]1=[O:34].C(=O)([O-])[O-].[K+].[K+].[NH4+].[Cl-].O>C(Cl)(Cl)Cl.CC(O)C.C(#N)C>[CH2:20]([N:8]1[CH2:9][CH2:10][N:11]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:12][C@@H:7]1[CH2:6][N:33]1[CH2:32][CH2:31][NH:30][C:29](=[O:34])[C:28]1([CH3:35])[CH3:27])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 2111572-Piperazinone, 3,3-dimethyl-HCID 57429219Ammonium chloride monohydrateHCID 86670397((2R)-1,4-dibenzyl-2-piperazinyl)methyl methanesulfonate

Product 1

HCID 665835354-(((2R)-1,4-dibenzyl-2-piperazinyl)methyl)-3,3-dimethyl-2-piperazinoneYield 59.8%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 6212ChloroformSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
130 °C

Procedure

A 20 ml, microwave vial was charged with ((2R)-1,4-dibenzyl-2-piperazinyl)methyl methanesulfonate (0.817 g, 2.18 mmol, Example 184, Step 1), 3,3-dimethylpiperazin-2-one (0.297 g, 2.32 mmol, ChemBridge, San Diego, Calif.), potassium carbonate (0.910 g, 6.58 mmol) and acetonitrile (10 mL). The vial was sealed and the reaction mixture was stirred at 130° C. for 30 min. The reaction was allowed to cool to room temperature then saturated aqueous NH4Cl/water (1:1) (100 mL) and 10% iPrOH in chloroform (100 mL) were added. The aqueous phase was extracted with 10% iPrOH in chloroform (2×50 mL). The combined organic phases were washed with saturated aqueous NaCl (200 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (50 g of silica gel, 0 to 10% iPrOH (with 10% NH4OH) in CHCl3) to afford 4-(((2R)-1,4-dibenzyl-2-piperazinyl)methyl)-3,3-dimethyl-2-piperazinone (0.53 g) as a white foam.

Workup

  1. customThe vial was sealed
  2. temperatureto cool to room temperature
  3. extractionThe aqueous phase was extracted with 10% iPrOH in chloroform (2×50 mL)
  4. washThe combined organic phases were washed with saturated aqueous NaCl (200 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by column chromatography (50 g of silica gel, 0 to 10% iPrOH (with 10% NH4OH) in CHCl3)

Sources & evidence

ORD record
ord-0b59e959963c457f80777cd3e296d2f1
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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