Binap, (A+-)- → 1-(2,4-Dimethoxyphenyl)-4-(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)piperazine

HRID 2063834Notes

Reaction equation

HRID 2063834 reaction equation
Br[C:2]1[C:3]([CH3:15])=[C:4]([CH3:14])[C:5]2[O:9][C:8]([CH3:11])([CH3:10])[CH2:7][C:6]=2[C:12]=1[CH3:13].[CH3:16][O:17][C:18]1[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:19]=1[N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[CH3:16][O:17][C:18]1[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:19]=1[N:26]1[CH2:27][CH2:28][N:29]([C:2]2[C:3]([CH3:15])=[C:4]([CH3:14])[C:5]3[O:9][C:8]([CH3:11])([CH3:10])[CH2:7][C:6]=3[C:12]=2[CH3:13])[CH2:30][CH2:31]1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 27362041-(2,4-dimethoxyphenyl)piperazineHCID 23676156Sodium t-butoxideHCID 667609285-Bromo-2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran

Product 1

HCID 594851091-(2,4-Dimethoxyphenyl)-4-(2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)piperazineYield 56%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To the toluene (10 mL) mixture solution of 5-bromo-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran (400 mg, 1.49 mmol) synthesized in Reference example 4, 1-(2,4-dimethoxyphenyl)piperazine (495 mg, 2.23 mmol), palladium acetate (17 mg, 0.0745 mmol) and BINAP (139 mg, 0.224 mmol), sodium t-butoxide (286 mg, 2.98 mmol) was added and stirred for 15 hours under reflux. After cooling to room temperature, water was added to the reaction solution, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue was purified by silica gel chromatography (hexane-ethyl acetate 95:5-85:15) and crystallized from ethyl acetate-hexane to obtain the title compound 340 mg (yield 56%). Melting point was 154 to 156° C.

Workup

  1. additionwas added
  2. temperatureunder reflux
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was removed by distillation under reduced pressure
  7. customThe residue was purified by silica gel chromatography (hexane-ethyl acetate 95:5-85:15)
  8. customcrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-f9d2933f4f6743aaa78cea114d2c14c7
Source dataset
uspto-grants-2012_10
Patent number
US08288390B2

Reaction notes

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