Peracetic Acid → Ethyl 6-(3-chloro-4-fluorobenzyl)-3,4-dihydroxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate

HRID 1817374Notes

Reaction equation

HRID 1817374 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[F:26])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:12]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[N:11][CH:10]=[C:9]([OH:21])[C:8]=2[C:7]1=[O:22].C([O-])(=[O:29])C.[Na+].C(OO)(=O)C.OS([O-])(=O)=O.[Na+]>C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][C:25]=1[F:26])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:12]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[N:11][C:10]([OH:29])=[C:9]([OH:21])[C:8]=2[C:7]1=[O:22]

Participants

6

Reactant 4

HCID 6585Peracetic AcidHCID 516919Sodium BisulfateHCID 517045Sodium AcetateHCID 59455599Ethyl 6-(3-chloro-4-fluorobenzyl)-4-hydroxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate

Product 1

HCID 178470321Ethyl 6-(3-chloro-4-fluorobenzyl)-3,4-dihydroxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of ethyl 6-(3-chloro-4-fluorobenzyl)-4-hydroxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate (5.0 g; see Example 12, Step 6) and sodium acetate (0.89 g) in acetic acid (90 mL) was added peracetic acid (28 mL). The mixture was then heated at 50° C. overnight. The mixture was cooled to 5° C. and saturated NaHSO4 (17 mL) added, keeping the temperature at less than 25° C. The mixture was concentrated to 50% original volume and partitioned between tert-butyl methyl ether (100 mL) and water (50 mL). The organic phase collected and the volatiles evaporated. The residue was dissolved in toluene (50 mL) and volatiles evaporated, the residue dissolved in toluene (50 mL) and evaporation repeated. Finally the residue was dissolved in toluene (20 mL). Acetic anhydride (3.9 mL) was added and the mixture heated at reflux until complete by HPLC analysis. The mixture cooled to ambient temperature and sodium ethoxide in ethanol (20 mL) was added. The reaction mixture stirred overnight. 2N HCl (31 mL) was added and the title product isolated by filtration.

Workup

  1. temperatureThe mixture was cooled to 5° C.
  2. customat less than 25° C
  3. concentrationThe mixture was concentrated to 50% original volume
  4. custompartitioned between tert-butyl methyl ether (100 mL) and water (50 mL)
  5. customThe organic phase collected
  6. customthe volatiles evaporated
  7. dissolutionThe residue was dissolved in toluene (50 mL)
  8. customvolatiles evaporated
  9. dissolutionthe residue dissolved in toluene (50 mL)
  10. customevaporation
  11. dissolutionFinally the residue was dissolved in toluene (20 mL)
  12. additionAcetic anhydride (3.9 mL) was added
  13. temperaturethe mixture heated
  14. temperatureat reflux until complete by HPLC analysis
  15. temperatureThe mixture cooled to ambient temperature
  16. additionsodium ethoxide in ethanol (20 mL) was added
  17. addition2N HCl (31 mL) was added

Sources & evidence

ORD record
ord-0347eb0dc38d4b5ab0d22c780f0b4a7f
Source dataset
uspto-grants-2009_10
Patent number
US07598264B2

Reaction notes

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