1,4-Dibromobenzene → 4-(4-Bromophenyl)-1-methyl-2-piperazinone

HRID 1052304Notes

Reaction equation

HRID 1052304 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][CH:3]=1.Cl.[CH3:10][N:11]1[CH2:16][CH2:15][NH:14][CH2:13][C:12]1=[O:17].C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([N:14]2[CH2:15][CH2:16][N:11]([CH3:10])[C:12](=[O:17])[CH2:13]2)=[CH:3][CH:4]=1

Participants

7

Reactant 3

HCID 78041,4-DibromobenzeneHCID 10796Cesium carbonateHCID 170607661-Methylpiperazin-2-one--hydrogen chloride (1/1)

Product 1

HCID 899635354-(4-Bromophenyl)-1-methyl-2-piperazinoneYield 96.6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 1,4-dibromobenzene (470 mg, 2.0 mmol), 1-methylpiperazin-2-one hydrochloride (150 mg, 1.0 mmol, from J&W PharmLab), palladium acetate (6.7 mg, 0.030 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.035 g, 0.060 mmol), and cesium carbonate (0.98 g, 3.0 mmol) in toluene (5.0 mL) was evacuated and refilled with nitrogen three times and then the reaction was stirred at 105° C. overnight. The mixture was diluted with ethyl acetate, washed with water, brine, then dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexane (0-60%) to afford the desired product (0.26 g, 49%). LCMS calculated for C11H14BrN2O (M+H)+: m/z=269.0. Found 269.0.

Workup

  1. customwas evacuated
  2. additionrefilled with nitrogen three times
  3. additionThe mixture was diluted with ethyl acetate
  4. washwashed with water, brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexane (0-60%)

Sources & evidence

ORD record
ord-37c336a856ac4539bbac69e60a34e007
Source dataset
uspto-grants-2016_07
Patent number
US09388185B2

Reaction notes

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