Ethyl Acetate → HCID 23081199, compound

HRID 856099Notes

Reaction equation

HRID 856099 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[CH:10][CH:9]=1.[F:20][C:21]([F:31])([F:30])[O:22][C:23]1[CH:28]=[CH:27][C:26](Br)=[CH:25][CH:24]=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:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:15][CH2:16][N:17]([C:26]3[CH:25]=[CH:24][C:23]([O:22][C:21]([F:20])([F:30])[F:31])=[CH:28][CH:27]=3)[CH2:18][CH2:19]2)=[CH:10][CH:9]=1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 5210081-Bromo-4-(trifluoromethoxy)benzeneHCID 230811571-[4-(Tetrahydropyran-2-yloxy)phenyl]piperazineHCID 23676156Sodium t-butoxide

Product 1

HCID 23081199HCID 23081199, compoundYield 91.2%

Reagents, catalysts & solvents 4

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

Procedure

A mixture of 1-[4-(tetrahydropyran-2-yloxy)phenyl]piperazine (2.1 g, 8.05 mmol) prepared in Reference Example 184, 4-trifluoromethoxy-1-bromobenzene (1.9 g, 8.05 mmol), palladium acetate (72 mg, 0.32 mmol), BINAP (300 mg, 0.48 mmol) and sodium tert-butoxide (1.0 g, 10.5 mmol) in toluene (30 ml) was refluxed under a nitrogen atmosphere for 5 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]-4-(4-trifluoromethoxyphenyl)piperazine (3.1 g, yield 90%) as a white powder.

Workup

  1. temperaturewas refluxed under a nitrogen atmosphere for 5 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-892e1928eb744cea86788614b5a5f33e
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

Loading…