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

HRID 322535Notes

Reaction equation

HRID 322535 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-pyridinone

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 (16-1; Aldrich; 22.97 g, 165 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, 165 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 (500 ml) and brine (500 ml), acidified to pH 1 with 1 M HCl (165 ml). The aqueous layer was extracted methylene chloride (two times) and the combined organic layers were washed with sodium hydrogen carbonate solution and brine, dried (Na2SO4) and evaporated in vacuo to a brown solid. This was recrystallized from methanol, to give the title compound 16-2 as a tan solid: 1H NMR (300 MHz, 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 (500 ml) and brine (500 ml)
  6. extractionThe aqueous layer was extracted methylene chloride (two times)
  7. washthe combined organic layers were washed with sodium hydrogen carbonate solution and brine
  8. dry with materialdried (Na2SO4)
  9. customevaporated in vacuo to a brown solid
  10. customThis was recrystallized from methanol

Sources & evidence

ORD record
ord-38f2d9eccaf24721acdd3b6454bb8f5e
Source dataset
uspto-grants-2001_04
Patent number
US06211184B1

Reaction notes

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