Benzyl Alcohol → 3-benzyloxycarbonylamino-6-methyl-2-pyridinone

HRID 1378700Notes

Reaction equation

HRID 1378700 reaction equation
C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:8])=CC=1.[OH:18][C:19]1[C:24](C(O)=O)=[CH:23][CH:22]=[C:21]([CH3:28])[N:20]=1.C([N:31]([CH2:34]C)CC)C.[CH2:36]([OH:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>O1CCOCC1>[CH2:36]([O:43][C:34]([NH:31][C:24]1[C:19](=[O:18])[NH:20][C:21]([CH3:28])=[CH:22][CH:23]=1)=[O:8])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471Triethylamine2×HCID 199401P,P-Diphenylphosphinic azideHCID 178425908HCID 178425908, compound

Product 1

HCID 100838403-benzyloxycarbonylamino-6-methyl-2-pyridinoneYield 55%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

DPPA (35.6 ml, 165 mmol) was added to a stirred solution of 2-hydroxy-6-methylpyridine-3-carboxylic acid (22.97 g, 150 mmol) and triethylamine (23.0 ml, 165 mmol) in dry dioxane (300 ml) and the resulting solution was heated to reflux. After 16 h more triethylamine (23.0 ml, 165 mmol) and benzyl alcohol (17.1 ml, 150 mmol) were added and the solution was refluxed for a further 24 h. The reaction was concentrated in vacuo to remove most of the volatiles. The residue was partitioned between methylene chloride and brine, acidified to pH 1 with 1M HCl. The organic layer was washed with sodium hydrogen carbonate solution and brine, dried (MgSO4) and evaporated in vacuo. The crude product was purified by flash column chromatography (ethyl acetate/hexanes gradient 70-80% ethyl acetate, followed by 5% methanol/chloroform). The resulting solid was recrystallized from methanol, to give the title compound (21.15 g, 55%): 1H NMR (CDCl3) δ 2.29 (s, 3H, CH3), 5.20 (s, 2H, PhCH2), 6.06 (d, J=7.6 Hz, pyridinone-5-H), 7.32-7.43 (m, 5H, Ph), 7.67 (br s, 1H, CbzNH), 8.03 (br d, pyridinone-4-H).

Workup

  1. temperaturethe resulting solution was heated to reflux
  2. temperaturethe solution was refluxed for a further 24 h
  3. concentrationThe reaction was concentrated in vacuo
  4. customto remove most of the volatiles
  5. customThe residue was partitioned between methylene chloride and brine
  6. washThe organic layer was washed with sodium hydrogen carbonate solution and brine
  7. dry with materialdried (MgSO4)
  8. customevaporated in vacuo
  9. customThe crude product was purified by flash column chromatography (ethyl acetate/hexanes gradient 70-80% ethyl acetate, followed by 5% methanol/chloroform)
  10. customThe resulting solid was recrystallized from methanol

Sources & evidence

ORD record
ord-5eb37c0701f34b668226ac757b49bce4
Source dataset
uspto-grants-1997_09
Patent number
US05668289

Reaction notes

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