Methyl acetoacetate → Bacampicillin

HRID 478049

Reaktionsgleichung

Reaktionsgleichung von HRID 478049
[CH3:1][C:2]1([CH3:24])[S:6][C@@H:5]2[C@H:7]([NH:10][C:11]([C@H:13]([NH2:20])[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)=[O:12])[C:8](=[O:9])[N:4]2[C@H:3]1[C:21]([OH:23])=[O:22].O.O.O.COC(=O)CC(C)=O.C(=O)(O)[O-].[Na+].[C:41](=[O:49])([O:46][CH2:47][CH3:48])[O:42][CH:43](Br)[CH3:44]>C(OCC)(=O)C.O.CC(C)=O.C(N(CC)CC)C>[CH3:44][CH2:43][O:42][C:41]([O:46][CH:47]([O:22][C:21]([C@@H:3]1[N:4]2[C:8]([C@@H:7]([NH:10][C:11]([C@H:13]([NH2:20])[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:12])[C@H:5]2[S:6][C:2]1([CH3:24])[CH3:1])=[O:9])=[O:23])[CH3:48])=[O:49]

Komponenten

9

Edukt 4

HCID 7757Methyl acetoacetateHCID 23565Ampicillin TrihydrateHCID 516892Sodium BicarbonateHCID 30215501-Bromoethyl ethyl carbonate

Produkt 1

HCID 441397BacampicillinAusbeute 67 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 180AcetoneLösungsmittel2×HCID 962WaterLösungsmittelHCID 8471TriethylamineLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

A mixture of ampicillin trihydrate (15 g), methylaceto acetate (5.65 g), triethylamine (4.05 g) and acetone (7.5 ml) was stirred at 40° C. for 3 hours. Acetone (30 ml) and sodium bicarbonate (12.4 g) were added. 1-Bromoethyl ethyl carbonate (14.6 g) was added dropwise during 1 hour. Stirring was continued at 40° C. for 1 hour. Water (37.5 ml) was added and the reaction was stirred at 20° C. for 1 hour. Ethyl acetate (37.5 ml) was added and the phases separated. The organic phase was washed with 20% sodium chloride solution. Acetone (7.5 ml) was added and a solution of ca. 16% hydrochloric acid was added slowly until a stable pH of 2.2 was obtained. The addition takes 11/2-2 hours. The solution was dried over anhydrous sodium sulfate and filtered. Butyl acetate (45 ml) was added and the solution was evaporated in vacuo to remove most of the solvents (bath temperature 35° C.). More butyl acetate (50 ml) was added and partially distilled. The resulting slurry was cooled for several hours and filtered to give 11.6 g bacampicillin.

Aufarbeitung

  1. stirringStirring
  2. waitwas continued at 40° C. for 1 hour
  3. stirringthe reaction was stirred at 20° C. for 1 hour
  4. customthe phases separated
  5. washThe organic phase was washed with 20% sodium chloride solution
  6. additionAcetone (7.5 ml) was added
  7. additiona solution of ca. 16% hydrochloric acid was added slowly until a stable pH of 2.2
  8. customwas obtained
  9. additionThe addition
  10. custom2-2 hours
  11. dry with materialThe solution was dried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. additionButyl acetate (45 ml) was added
  14. customthe solution was evaporated in vacuo
  15. customto remove most of the solvents (bath temperature 35° C.)
  16. additionMore butyl acetate (50 ml) was added
  17. distillationpartially distilled
  18. temperatureThe resulting slurry was cooled for several hours
  19. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-743f45a0d4124d639956a7549ffcf5a7
Quelldatensatz
uspto-grants-1989_12
Patentnummer
US04889929

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