p-Bromochlorobenzene → Tert-butyl 4-(4-chlorophenylamino)piperidine-1-carboxylate

HRID 856072Notes

Reaction equation

HRID 856072 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][CH:3]=1.[NH2:9][CH:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]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>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([NH:9][CH:10]2[CH2:11][CH2:12][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:14][CH2:15]2)=[CH:3][CH:4]=1

Participants

9

Reactant 4

HCID 7806p-BromochlorobenzeneHCID 8857Ethyl AcetateHCID 12682914-Amino-1-Boc-piperidineHCID 23676156Sodium t-butoxide

Product 1

HCID 1491503Tert-butyl 4-(4-chlorophenylamino)piperidine-1-carboxylateYield 86%

Reagents, catalysts & solvents 4

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

Procedure

A mixture of p-bromochlorobenzene (1.91 g, 9.99 mmol), tert-butyl 4-aminopiperidine-1-carboxylate (2.0 g, 9.99 mmol), palladium acetate (45 mg, 0.2 mmol), (R)-(+)-BINAP (187 mg, 0.3 mmol) and sodium tert-butoxide (1.35 g, 14.0 mmol) in toluene (20 ml) was refluxed under a nitrogen atmosphere for 1 hour. 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 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 (methylene chloride/methanol=100/1) to afford tert-butyl 4-(4-chlorophenylamino)piperidine-1-carboxylate (2.67 g, yield 86%) as a yellow powder.

Workup

  1. temperaturewas refluxed under a nitrogen atmosphere for 1 hour
  2. customthe insoluble substances were removed by filtration through Celite
  3. extractionthe filtrate was then 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 (methylene chloride/methanol=100/1)

Sources & evidence

ORD record
ord-c276d8dff44d4683981ae2411bdadb15
Source dataset
uspto-grants-2007_08
Patent number
US07262212B2

Reaction notes

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