Ethyl Acetate → HCID 67274513, compound

HRID 1695968Notes

Reaction equation

HRID 1695968 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH3:9])=[CH:4][CH:3]=1.Br[C:17]1[CH:29]=[CH:28][C:20]([O:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)=[CH:19][CH:18]=1.C(O[Na])(C)(C)C.C(OCC)(=O)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[O:23]1[CH2:24][CH2:25][CH2:26][CH2:27][CH:22]1[O:21][C:20]1[CH:28]=[CH:29][C:17]([N:13]2[CH2:14][CH2:15][CH:10]([N:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)[CH3:9])[CH2:11][CH2:12]2)=[CH:18][CH:19]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 46464362-(4-Bromophenoxy)tetrahydro-2H-pyranHCID 67274913HCID 67274913, compoundHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 67274513HCID 67274513, compoundYield 30%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

4-(N-(4-chlorophenyl)-N-methylamino)-piperidine (2.52 g, 11.22 mmol), 2-(4-bromophenoxy) tetrahydropyran (2.89 g, 11.22 mmol), palladium acetate (50 mg, 0.22 mmol), (S)-(−)-2,2-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) (212 mg, 0.34 mmol) and tert-butoxy sodium (1.51 g, 15.71 mmol) were refluxed with heating in toluene (30 ml) under nitrogen atmosphere for 3 hours. Ethyl acetate and water were added into the reaction solution and stirred, then the resulting precipitate was removed by filtration through Celite, thereafter the filtrate was extracted with ethyl acetate. The organic phase was washed with saturated brine, dried over magnesium sulfate, and then filtered. After the resulting filtrate was concentrated under reduced pressure, the residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=20/1) to afford 1-(4-(tetrahydropyran-2-yloxy)phenyl)-4-(N-(4-chlorophenyl)-N-methylamino)piperidine (1.33 g, yield 30%) as a light yellow powder.

Workup

  1. customthe resulting precipitate was removed by filtration through Celite
  2. extractionthe filtrate was extracted with ethyl acetate
  3. washThe organic phase was washed with saturated brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationAfter the resulting 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-572926d884864f52bdc3a005d9627b34
Source dataset
uspto-grants-2012_04
Patent number
US08163753B2

Reaction notes

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