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

HRID 48872Notes

Reaction equation

HRID 48872 reaction equation
C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:8])C=CC=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 56%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Diphenylphosphoryl azide (11.9 mL, 55 mmol) was added to a solution of 2-hydroxy-6-methylpyridine-3-carboxylic acid (7.65 g, 50 mmol) and triethylamine (7.7 mL, 55 mmol) in dry dioxane (100 mL) and the resulting solution was heated to reflux. After 16 h more triethylamine (7.7 mL, 55 mmol) and benzyl alcohol (5.7 mL, 50 mmol) were added and the solution was refluxed for a further 24 h. The reaction mixture was concentrated in vacuo and the residue was partitioned between methylene chloride (200 mL) and brine (100 mL), acidified to pH 1 with 10% HCl. The organic layer was washed with saturated NaHCO3 (2×100 mL), brine (100 mL), dried over Na2SO4 and filtered. After evaporating the solvent in vacuo, methanol (100 mL) and hexane (20 mL) were added to the residue, the solid was collected, washed with methanol (50 mL) and dried to give the title compound as a white solid (7.2 g, 56%). 1H-NMR (300 MHz, CDCl3) δ12.82 (s, 1H), 8.06 (d, J=7.0 Hz, 1H), 7.69 (s, 1H), 7.42 (m, 5H), 6.09 (d, J=7.5 Hz, 1H), 5.22 (s, 2H), 2.32 (s, 3H).

Workup

  1. temperaturethe resulting solution was heated to reflux
  2. temperaturethe solution was refluxed for a further 24 h
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customthe residue was partitioned between methylene chloride (200 mL) and brine (100 mL)
  5. washThe organic layer was washed with saturated NaHCO3 (2×100 mL), brine (100 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customAfter evaporating the solvent in vacuo, methanol (100 mL) and hexane (20 mL)
  9. additionwere added to the residue
  10. customthe solid was collected
  11. washwashed with methanol (50 mL)
  12. customdried

Sources & evidence

ORD record
ord-9dfb0035874e4387a915f152d032b455
Source dataset
uspto-grants-2004_03
Patent number
US06706021B2

Reaction notes

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