Ethyl Acetate → HCID 23081427, compound

HRID 856070Notes

Reaction equation

HRID 856070 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.[NH2:13][CH:14]1[CH2:19][CH2:18][N:17]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:16][CH2:15]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=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH2:20]([N:17]1[CH2:18][CH2:19][CH:14]([NH:13][C:2]2[CH:7]=[CH:6][C:5]([O:8][C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=2)[CH2:15][CH2:16]1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

9

Reactant 4

HCID 8857Ethyl AcetateHCID 4158521-Benzyl-4-piperidylamineHCID 5210081-Bromo-4-(trifluoromethoxy)benzeneHCID 23676156Sodium t-butoxide

Product 1

HCID 23081427HCID 23081427, compoundYield 103.2%

Reagents, catalysts & solvents 4

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

Procedure

A mixture of 1-bromo-4-trifluoromethoxybenzene (2.0 g, 8.3 mmol), 4-amino-1-benzylpiperidine (1.73 g, 9.13 mmol), palladium acetate (37 mg, 0.17 mmol), (R)-(+)-BINAP (155 mg, 0.25 mmol) and sodium tert-butoxide (1.2 g, 11.6 mmol) in toluene (30 ml) was refluxed under a nitrogen atmosphere for 5 hours. Ethyl acetate and water were added to the reaction mixture while stirring, the insoluble substances were removed by filtration through Celite, and the filtrate was extracted with ethyllacetate. 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 (methylene chloride/methanol=100/1) to afford (1-benzylpiperidin-4-yl)-(4-trifluoromethoxyphenyl)amine (3.0 g, yield 99%) as a dark oil.

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 ethyllacetate
  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 (methylene chloride/methanol=100/1)

Sources & evidence

ORD record
ord-8b1deff0ad1d4d40b7ad9a167f36ebce
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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