Benzene, 1-bromo-2,4-dimethyl- → HCID 67381065, compound

HRID 1804412Notes

Reaction equation

HRID 1804412 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[CH3:9].[C:10]([N:17]1[CH2:22][CH2:21][NH:20][C@H:19]([CH3:23])[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][N:20]([C:2]2[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=2[CH3:9])[C@H:19]([CH3:23])[CH2:18]1)=[O:11])([CH3:16])([CH3:14])[CH3:15]

Participants

7

Reactant 4

HCID 68503Benzene, 1-bromo-2,4-dimethyl-HCID 2756811(R)-1-Boc-3-methylpiperazineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxide

Product 1

HCID 67381065HCID 67381065, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

To a mixture of 1-bromo-2,4-dimethylbenzene (3.8 mL), (R)-4-N-Boc-2-methylpiperazine (5.0 g), palladium (II) acetate (281 mg), 2-(dicyclohexylphosphino)-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (1.19 g) and sodium tert-butoxide (3.4 g) was added toluene (50 mL), and the mixture was refluxed for 3 hr. After cooling, the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated. The residue was purified by column chromatography (chloroform) to give (R)-4-(2,4-dimethylphenyl)-3-methylpiperazine-1-carboxylic acid tert-butyl ester. The compound was dissolved in chloroform (8.0 mL), 4N hydrogen chloride/ethyl acetate (8.0 mL) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was alkalified, and extracted with chloroform. The organic layer was evaporated to give (R)-1-(2,4-dimethylphenyl)-2-methylpiperazine (1.2 g).

Workup

  1. temperaturethe mixture was refluxed for 3 hr
  2. temperatureAfter cooling
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. customthe solvent was evaporated
  6. customThe residue was purified by column chromatography (chloroform)

Sources & evidence

ORD record
ord-2ffb9d8fdb4e4631ac0018c965279fc8
Source dataset
uspto-grants-2013_01
Patent number
US08354401B2

Reaction notes

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