Acetic Acid → Ethyl 4-Ethoxy-2-oxo-1,2-dihydropyridine-3-carboxylate

HRID 408032Notes

Reaction equation

HRID 408032 reaction equation
C([C:3](=[C:9]([O:15][CH2:16][CH3:17])/[CH:10]=[CH:11]/[N:12](C)[CH3:13])[C:4]([O:6][CH2:7][CH3:8])=[O:5])#N.C(O)(=[O:20])C>>[CH2:16]([O:15][C:9]1[CH:10]=[CH:11][NH:12][C:13](=[O:20])[C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH3:17]

Participants

3

Reactant 2

HCID 176Acetic AcidHCID 86659920(4E)-Ethyl 2-cyano-5-(dimethylamino)-3-ethoxypenta-2,4-dienoate

Product 1

HCID 53393185Ethyl 4-Ethoxy-2-oxo-1,2-dihydropyridine-3-carboxylateYield 58.5%

Conditions

Temperature
100 °C

Procedure

(4E)-Ethyl 2-cyano-5-(dimethylamino)-3-ethoxypenta-2,4-dienoate (20 kg) and acetic acid (126 L) were charged to a reactor and heated to 100° C. for 3 hrs until the reaction was complete as characterized by HPLC. The reaction mass was cooled to 55° C. and acetic acid was removed by vacuum distillation at 65-75° C. After distillation, the mixture was cooled to room temperature and water (3 L) was added. The pH of the mixture was adjusted to 8 by addition of 100 L of a 30% sodium carbonate solution. The solids were filtered off and washed with 10 L of water. The combined aqueous layers were extracted three times with DCM (100 L). The combined DCM layers were washed with brine, then dried over sodium sulfate and concentrated to dryness. Ethyl acetate was added to the concentrate. The mixture was heated to 40° C. and then cooled to 25° C. The solids were filtered off, washed with petroleum ether and dried at room temperature for 12 hrs to yield ethyl 4-ethoxy-2-oxo-1,2-dihydropyridine-3-carboxylate (10.3 kg; 58.5% yield).

Workup

  1. temperatureThe reaction mass was cooled to 55° C.
  2. customacetic acid was removed by vacuum distillation at 65-75° C
  3. distillationAfter distillation
  4. temperaturethe mixture was cooled to room temperature
  5. additionwater (3 L) was added
  6. additionThe pH of the mixture was adjusted to 8 by addition of 100 L of a 30% sodium carbonate solution
  7. filtrationThe solids were filtered off
  8. washwashed with 10 L of water
  9. extractionThe combined aqueous layers were extracted three times with DCM (100 L)
  10. washThe combined DCM layers were washed with brine
  11. dry with materialdried over sodium sulfate
  12. concentrationconcentrated to dryness
  13. additionEthyl acetate was added to the concentrate
  14. temperatureThe mixture was heated to 40° C.
  15. temperaturecooled to 25° C
  16. filtrationThe solids were filtered off
  17. washwashed with petroleum ether
  18. customdried at room temperature for 12 hrs

Sources & evidence

ORD record
ord-b77c827c460048d7a72a05796a95f660
Source dataset
uspto-grants-2014_06
Patent number
US08754230B2

Reaction notes

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