Phenyl chloroformate → 2-ethyl-4-oxo-3,4-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 217224Notes

Reaction equation

HRID 217224 reaction equation
C[O:2][C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.Cl[C:10]([O:12][C:13]1[CH:18]=CC=C[CH:14]=1)=[O:11].[CH3:19][CH2:20][Mg+].[Br-].[CH3:23]C([O-])(C)C.[K+]>C1COCC1.CCOCC>[C:13]([O:12][C:10]([N:6]1[CH:7]=[CH:8][C:3](=[O:2])[CH2:4][CH:5]1[CH2:19][CH3:20])=[O:11])([CH3:14])([CH3:18])[CH3:23]

Participants

7

Reactant 4

HCID 15891Phenyl chloroformateHCID 692784-MethoxypyridineHCID 23665647Potassium tert-butoxideHCID 178461630HCID 178461630, compound

Product 1

HCID 426456702-ethyl-4-oxo-3,4-dihydro-2H-pyridine-1-carboxylic acid tert-butyl esterYield 86.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
10 °C

Procedure

To a solution of 4-methoxypyridine (15.6 g, 143 mmol) in dry THF (1 L) cooled to −35° C. is added ClCO2Ph (22.7 g, 144 mmol). After stirring the slurry for 1 hour, EtMgBr (150 mL, 150 mmol) is added slowly over 30 min. The mixture is warmed to 10° C. over 2 hours then quenched with H2O. The reaction mixture is extracted twice with Et2O (1 L), combined organic layer is dried over Na2SO4, and the solvent is removed under reduced pressure. To a solution of the resultant colorless oil in dry THF (500 mL) at −78° C. is added t-BuOK (64 g, 572 mmol). The reaction mixture is stirred overnight and warmed to room temperature. The reaction mixture is diluted with Et2O, quenched with ice, partitioned, and the organic layer is washed three times with 1.5 N aqueous NaOH and then with brine, dried over MgSO4 and concentrated in reduced pressure to afford 2-ethyl-4-oxo-3,4-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester as a pale yellow oil (27.8 g, 86% yield); ESI-MS m/z: 226 [M+1]+, Retention time 1.64 min (condition A).

Workup

  1. customthen quenched with H2O
  2. extractionThe reaction mixture is extracted twice with Et2O (1 L)
  3. dry with materialis dried over Na2SO4
  4. customthe solvent is removed under reduced pressure
  5. stirringThe reaction mixture is stirred overnight
  6. temperaturewarmed to room temperature
  7. customquenched with ice
  8. custompartitioned
  9. washthe organic layer is washed three times with 1.5 N aqueous NaOH
  10. dry with materialwith brine, dried over MgSO4
  11. concentrationconcentrated in reduced pressure

Sources & evidence

ORD record
ord-b2499fe0824b4839b0bd24d659056742
Source dataset
uspto-grants-2012_06
Patent number
US08193349B2

Reaction notes

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