Piperazine → 1-[4-(Tetrahydropyran-2-yloxy)phenyl]piperazine

HRID 856098Notes

Reaction equation

HRID 856098 reaction equation
Br[C:2]1[CH:14]=[CH:13][C:5]([O:6][CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][O:8]2)=[CH:4][CH:3]=1.[NH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1.CC(C)([O-])C.[Na+].C(OCC)(=O)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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.O>[O:8]1[CH2:9][CH2:10][CH2:11][CH2:12][CH:7]1[O:6][C:5]1[CH:13]=[CH:14][C:2]([N:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)=[CH:3][CH:4]=1

Participants

9

Reactant 4

HCID 4837PiperazineHCID 8857Ethyl AcetateHCID 46464362-(4-Bromophenoxy)tetrahydro-2H-pyranHCID 23676156Sodium t-butoxide

Product 1

HCID 230811571-[4-(Tetrahydropyran-2-yloxy)phenyl]piperazineYield 85.5%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of 2-(4-bromophenoxy)-tetrahydropyran (7.8 g, 30.3 mmol), piperazine (15.7 g, 180 mmol), palladium acetate (136 mg, 0.61 mmol), BINAP (567 mg, 0.91 mmol) and sodium tert-butoxide (3.8 g, 39.4 mmol) in toluene (50 ml) was refluxed under a nitrogen atmosphere for 2 hours. Ethyl acetate and water were added to the reaction mixture, which was stirred for a while. The insoluble substances were removed by filtration through Celite, and the filtrate was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=20/1) to afford 1-[4-(tetrahydropyran-2-yloxy)phenyl]piperazine (6.8 g, yield 85%) as a pale gray powder.

Workup

  1. temperaturewas refluxed under a nitrogen atmosphere for 2 hours
  2. customThe insoluble substances were removed by filtration through Celite
  3. extractionthe filtrate was extracted with ethyl acetate
  4. washThe extract was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=20/1)

Sources & evidence

ORD record
ord-af04fcd05612478aaad5002da02aa3ee
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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