Nitrogen → tert-Butyl 2,6-diethyl-4-oxopiperidine-1-carboxylate

HRID 217225Notes

Reaction equation

HRID 217225 reaction equation
N#N.[CH3:3][CH2:4][Mg+].[Br-].B(F)(F)F.CCOCC.[C:16]([O:20][C:21]([N:23]1[CH:28]=[CH:27][C:26](=[O:29])[CH2:25][CH:24]1[CH2:30][CH3:31])=[O:22])([CH3:19])([CH3:18])[CH3:17]>[Cu]I.O1CCCC1>[C:16]([O:20][C:21]([N:23]1[CH:24]([CH2:30][CH3:31])[CH2:25][C:26](=[O:29])[CH2:27][CH:28]1[CH2:4][CH3:3])=[O:22])([CH3:19])([CH3:18])[CH3:17]

Participants

7

Reactant 4

HCID 947NitrogenHCID 8000Boron trifluoride etherateHCID 426456702-ethyl-4-oxo-3,4-dihydro-2H-pyridine-1-carboxylic acid tert-butyl esterHCID 178461630HCID 178461630, compound

Product 1

HCID 44558577tert-Butyl 2,6-diethyl-4-oxopiperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To CuI (0.82 mmol, 156 mg) in a flask purged with N2 is added 1.00 M tetrahydrofuran solution of EtMgBr (0.82 mmol, 0.82 ml) at −78° C. After stirring the suspension for 30 min, BF3.Et2O (0.41 mmol, 57.9 mg) is added and stirred for 10 min at the same temperature. To the suspension is added tetrahydrofuran solution (3.3 mL) of 2-ethyl-4-oxo-3,4-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (0.41 mmol, 92.7 mg) at −78° C., then the mixture is allowed to stir for 1.5 hours and then allow to stir at −40° C. for 2 hours. The mixture is warmed to room temperature and quenched with saturated aqueous NH4Cl and extracted with EtOAc. The combined organic layers are washed with brine, dried over MgSO4, filtered, concentrated under reduced pressure, and purified by silica gel column chromatography (eluent: hexane/EtOAc=10/1) and separated the cis and trans isomers of racemic 2,6-diethyl-4-oxo-piperidine-1-carboxylic acid tert-butyl ester (50 mg, 50%); ESI-MS m/z: 200 [M-tBu+2]+, Retention time 3.51 min. (condition A).

Workup

  1. stirringstirred for 10 min at the same temperature
  2. stirringto stir for 1.5 hours
  3. stirringto stir at −40° C. for 2 hours
  4. customquenched with saturated aqueous NH4Cl
  5. extractionextracted with EtOAc
  6. washThe combined organic layers are washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. custompurified by silica gel column chromatography (eluent: hexane/EtOAc=10/1)
  11. customseparated the cis and trans isomers of racemic 2,6-diethyl-4-oxo-piperidine-1-carboxylic acid tert-butyl ester (50 mg, 50%)

Sources & evidence

ORD record
ord-5e3453b4e2e04e2786b256ad04d6a58f
Source dataset
uspto-grants-2012_06
Patent number
US08193349B2

Reaction notes

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