Hydroquinone → Tert-butyl 4-(pyridin-4-yl)piperidine-1-carboxylate

HRID 1829189Notes

Reaction equation

HRID 1829189 reaction equation
I[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.C1(C=CC(O)=CC=1)O.Br[C:24]1[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1>CN(C)C=O.[Zn].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].ClCCl>[N:27]1[CH:28]=[CH:29][C:24]([CH:2]2[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]2)=[CH:25][CH:26]=1

Participants

9

Reactant 4

HCID 785HydroquinoneHCID 142684-BromopyridineHCID 521585Tris(furan-2-yl)phosphaneHCID 10892302Tert-butyl 4-iodopiperidine-1-carboxylate

Product 1

HCID 22061398Tert-butyl 4-(pyridin-4-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent3×HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

Dichloromethane (0.1 ml) was added to a suspension of zinc (2 g, 31.7 mmol) in N,N-dimethylformamide (5 ml), and the mixture warmed until gas evolution occurred. tert-Butyl 4-iodo-1-piperidinecarboxylate (EP 1078928) (4.9 g, 15.8 mmol), and hydroquinone (35 mg, 0.32 mmol) in N,N-dimethylformamide (5 ml) was added, and the mixture warmed until an exotherm was evident. 4-Bromopyridine (1 g, 6.33 mmol), tris(dibenzylideneacetone)dipalladium (0) (73 mg, 0.127 mmol) and tri(2-furyl)phosphine (59 mg, 0.25 mmol) in N,N-dimethylformamide (5 ml) were added, and the reaction stirred at 60° C. for 30 minutes. The cooled mixture was partitioned between water (100 ml) and diethyl ether (50 ml), and the layers separated. The aqueous phase was extracted with diethyl ether (2×50 ml), the combined organic solutions washed with brine (50 ml), dried (MgSO4) and evaporated under reduced pressure, to give a brown oil. This was purified by column chromatography on silica gel using ethyl acetate:pentane (50:50) as eluant to afford the title compound as a yellow oil, 1.1 g.

Workup

  1. temperaturethe mixture warmed until gas evolution
  2. temperaturethe mixture warmed until an exotherm
  3. customThe cooled mixture was partitioned between water (100 ml) and diethyl ether (50 ml)
  4. customthe layers separated
  5. extractionThe aqueous phase was extracted with diethyl ether (2×50 ml)
  6. washthe combined organic solutions washed with brine (50 ml)
  7. dry with materialdried (MgSO4)
  8. customevaporated under reduced pressure
  9. customto give a brown oil
  10. customThis was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-984ff417fd034aeeabbc420c0dcfe2f0
Source dataset
uspto-grants-2006_06
Patent number
US07060836B2

Reaction notes

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