Ethyl isonicotinate → Tert-butyl 4-[2-oxo-2-(4-pyridinyl)ethyl]-2-pyridinylcarbamate

HRID 23529

Reaction equation

HRID 23529 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:3]=1.C([Li])CCC.[C:21](OCC)(=[O:28])[C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1>C1COCC1>[O:28]=[C:21]([C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1)[CH2:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])[CH:3]=1

Participants

5

Reactant 3

HCID 15291Ethyl isonicotinateHCID 11063648tert-butyl N-(4-methylpyridin-2-yl)carbamateHCID 178418339Butyllithium

Product 1

HCID 22574132Tert-butyl 4-[2-oxo-2-(4-pyridinyl)ethyl]-2-pyridinylcarbamateYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Tert-butyl 4-methyl-2-pyridinylcarbamate (Ihle, N. C.; Krause, A. E.; J. Org. Chem., 1996, 61(14):4810-4811; 10 g, 48.0 mmol) was dissolved in 100 mL THF and cooled to −78° C. under argon and was treated with n-butyllithium (2.5-M in hexanes, 48.0 mL, 120 mmol) such that the internal temperature did not exceed −50° C. The reaction was warmed to 20° C. for 20 min. then was recooled to −78° C. and ethyl isonicotinate (10.79 mL, 72.0 mmol) was added neat and the reaction again was warmed to 20° C. and stirred 45 minutes. The reaction was quenched with sat. NaHCO3 and extracted with ethyl acetate. The organics were dried over Na2SO4, filtered and concentrated under reduced pressure to give a red-orange oil which was purified by silica gel chromatography, eluting from 50% ethyl acetate in hexanes to 100% ethyl acetate to afford 7.56 g (50%) of the titled compound as a yellow oil.

Workup

  1. customdid not exceed −50° C
  2. temperatureThe reaction was warmed to 20° C. for 20 min.
  3. customthen was recooled to −78° C.
  4. customthe reaction
  5. temperatureagain was warmed to 20° C.
  6. customThe reaction was quenched with sat. NaHCO3
  7. extractionextracted with ethyl acetate
  8. dry with materialThe organics were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto give a red-orange oil which
  12. customwas purified by silica gel chromatography
  13. washeluting from 50% ethyl acetate in hexanes to 100% ethyl acetate

Sources & evidence

ORD record
ord-b940d94cb9ee406c94a5574093dec312
Source dataset
uspto-grants-2005_02
Patent number
US06852727B2

Linked notes

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