1-Bromo-4-fluorobenzene → tert-Butyl 4-(4-fluoroanilino)piperidine-1-carboxylate

HRID 1477580Notes

Reaction equation

HRID 1477580 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.Br[C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C(C)=CC=CC=1>[F:22][C:19]1[CH:20]=[CH:21][C:16]([NH:1][CH:2]2[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]2)=[CH:17][CH:18]=1

Participants

6

Reactant 3

HCID 99931-Bromo-4-fluorobenzeneHCID 12682914-Amino-1-Boc-piperidineHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl

Product 1

HCID 16413902tert-Butyl 4-(4-fluoroanilino)piperidine-1-carboxylateYield 72.8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 7237O-XyleneSolvent

Procedure

Under a nitrogen atmosphere, a xylene solution (65 mL) of tert-butyl 4-amino-piperidine-1-carboxylate (1.00 g, 5.00 mmol), 4-bromo-1-fluorobenzene (0.500 mL, 4.57 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethyl-[1,1′-biphenyl]-2-amine (360 mg, 1.00 mmol), and tris(dibenzylideneacetone)dipalladium (0) (209 mg, 0.250 mmol) was stirred at 140° C. for 4 hours. After completion of the reaction, the reaction solution was concentrated under reduced pressure and purified by silica gel column chromatography (hexane/ethyl acetate=100/0→70/30 (v/v)) to obtain the title compound (980 mg, yield 66%).

Workup

  1. customAfter completion of the reaction
  2. concentrationthe reaction solution was concentrated under reduced pressure
  3. custompurified by silica gel column chromatography (hexane/ethyl acetate=100/0→70/30 (v/v))

Sources & evidence

ORD record
ord-29344fb506244a22afe413519460364c
Source dataset
uspto-grants-2016_08
Patent number
US09403798B2

Reaction notes

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