Ethyl Acetate → Tert-butyl 4-[3-(tetrahydropyran-2-yloxy)phenyl]piperazine-1-carboxylate

HRID 856110Notes

Reaction equation

HRID 856110 reaction equation
[N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Br[C:15]1[CH:16]=[C:17]([CH:25]=[CH:26][CH:27]=1)[O:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]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:20]1[CH2:21][CH2:22][CH2:23][CH2:24][CH:19]1[O:18][C:17]1[CH:16]=[C:15]([N:4]2[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]2)[CH:27]=[CH:26][CH:25]=1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 50672642-(3-Bromophenoxy)tetrahydro-2H-pyranHCID 23676156Sodium t-butoxide

Product 1

HCID 23081281Tert-butyl 4-[3-(tetrahydropyran-2-yloxy)phenyl]piperazine-1-carboxylateYield 101.5%

Reagents, catalysts & solvents 4

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

Procedure

A mixturte of tert-butyl piperazine-1-carboxylate (2.94 g, 15.8 mmol), 2-(3-bromophenoxy)tetrahydropyran (3.69 g, 14.4 mmol), palladium acetate (64 mg, 0.29 mmol), BINAP (285 mg, 0.43 mmol) and sodium tert-butoxide (1.8 g, 18.7 mmol) in toluene (40 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 then 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 tert-butyl 4-[3-(tetrahydropyran-2-yloxy)phenyl]piperazine-1-carboxylate (5.3 g, yield 99%) as a colorless oil.

Workup

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

Sources & evidence

ORD record
ord-8ba1ce3a74274eb3815b56de94c871fc
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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