tert-Butyl piperazine-1-carboxylate → HCID 71251974, compound

HRID 2411236Notes

Reaction equation

HRID 2411236 reaction equation
Cl[C:2]1[C:7]([CH3:8])=[N:6][C:5]([CH3:9])=[CH:4][N:3]=1.[C:10]([N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC(C)([O-])C.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[C:13]([O:12][C:10]([N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH:18]1[C:2]1[C:7]([CH3:8])=[N:6][C:5]([CH3:9])=[CH:4][N:3]=1)=[O:11])([CH3:16])([CH3:14])[CH3:15]

Participants

7

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 116726802-Chloro-3,5-dimethylpyrazineHCID 23676156Sodium t-butoxide

Product 1

HCID 71251974HCID 71251974, compoundYield 87.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

Under a nitrogen stream, to a mixture of 2-chloro-3,5-dimethylpyrazine (2.8 g), 1-Boc-piperazine (3.7 g), palladium(II) acetate (225 mg), 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropyl-1,1′-biphenyl (953 mg) and sodium tert-butoxide (2.7 g) was added toluene (40 mL), and the mixture was stirred with heating under reflux for 8 hr. After cooling, the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The obtained residue was purified by column chromatography (hexane:ethyl acetate) to give (3,5-dimethylpyrazin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (5 g). The obtained (3,5-dimethylpyrazin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (5 g) was dissolved in chloroform (15 mL), 4N hydrogen chloride/ethyl acetate (15 mL) was added, and the mixture was stirred at room temperature overnight. To the reaction mixture was added ethyl acetate (100 mL), and the precipitate was collected by filtration to give the title compound (3.3 g).

Workup

  1. temperaturewith heating
  2. temperatureunder reflux for 8 hr
  3. temperatureAfter cooling
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. customthe solvent was evaporated
  7. customThe obtained residue was purified by column chromatography (hexane:ethyl acetate)

Sources & evidence

ORD record
ord-7363961c28bc469395e6300c7e60ef23
Source dataset
uspto-grants-2014_08
Patent number
US08816079B2

Reaction notes

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