Acetic Acid → (3S,11AR)-6-methoxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydrooxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxylic acid

HRID 338620Notes

Reaction equation

HRID 338620 reaction equation
CO[CH:3]([O:21][CH3:22])[CH2:4][N:5]1[C:10]([C:11]([O:13]C)=O)=[C:9]([O:15][CH3:16])[C:8](=[O:17])[C:7]([C:18]([OH:20])=[O:19])=[CH:6]1.CC(O)=O.CS(O)(=O)=O.[NH2:32][C@H:33](CO)[CH3:34]>CC#N>[CH3:34][C@@H:33]1[N:32]2[C:11](=[O:13])[C:10]3[N:5]([CH:6]=[C:7]([C:18]([OH:20])=[O:19])[C:8](=[O:17])[C:9]=3[O:15][CH3:16])[CH2:4][C@H:3]2[O:21][CH2:22]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6395Methanesulfonic AcidHCID 80307L-AlaninolHCID 534690001-(2,2-Dimethoxyethyl)-5-methoxy-6-(methoxycarbonyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid

Product 1

HCID 56926026(3S,11AR)-6-methoxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydrooxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
61.5 °C

Procedure

1-[2,2-bis(methyloxy)ethyl]-5-(methyloxy)-6-[(methyloxy)carbonyl]-4-oxo-1,4-dihydro-3-pyridinecarboxylic acid (22.54 g) was dissolved in 220 mL of CH3CN. HOAc (20 mL) and CH3SO3H (1.4 mL) were added at room temperature and the mixture was heated to 58-65° C. for 19.5 h. Alaninol (7.511 g) in CH3CN (15 mL) was added slowly and the resultant mixture was stirred at 64° C. for 18.5 h. The mixture was concentrated, and the residue was redissolved in CH2Cl2 (170 mL). HCl (1 N, 170 mL) was added and the layers were separated. The aqueous layer was extracted with CH2Cl2 (170 mL×2) and the organic layers were combined and concentrated. MeOH (50 mL) was added and the resultant mixture was again concentrated. MeOH (80 mL) was added and the resultant mixture was heated at reflux for 4 h, gradually cooled to 20° C. and held at 20° C. for 15 h. The product was collected by filtration and dried under vacuum.

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionthe residue was redissolved in CH2Cl2 (170 mL)
  3. additionHCl (1 N, 170 mL) was added
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with CH2Cl2 (170 mL×2)
  6. concentrationconcentrated
  7. additionMeOH (50 mL) was added
  8. concentrationthe resultant mixture was again concentrated
  9. additionMeOH (80 mL) was added
  10. temperaturethe resultant mixture was heated
  11. temperatureat reflux for 4 h
  12. temperaturegradually cooled to 20° C.
  13. filtrationThe product was collected by filtration
  14. customdried under vacuum

Sources & evidence

ORD record
ord-79d62fbf731f48fd98d18aa409e5cc0d
Source dataset
uspto-grants-2014_11
Patent number
US08889877B2

Reaction notes

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