Dimethylformamide → Cephalosporanic Acid

Temperature

40 °C

Phosphorus oxychloride (0.89 g.) and dry dimethylformamide (0.44 g.) were mixed under ice-cooling and then warmed for 30 minutes at 40° C. Dry methylene chloride (20 ml.) was added thereto and then distilled off. To the residue were added dry ethyl acetate (10 ml.) and then 2-methoxyimino-2-[2-(2,2,2-trifluoroacetamido)-1,3-thiazol-4-yl]acetic acid (syn isomer) (1.8 g.) with stirring and ice-cooling. The mixture was stirred for 40 minutes at the same temperature to give clear solution. On the other hand, trimethylsilylacetamide (6.36 g.) was added to a suspension of 7-aminocephalosporanic acid (1.65 g.) in dry ethyl acetate (25 ml.) with stirring at ambient temperature, after which the mixture was stirred for 1 hour to give a clear solution. To this solution was at a time added the above-obtained ethyl acetate solution with stirring at -20° to -25° C., and the resulting mixture was stirred for 2 hours at the same temperature. Water (30 ml.) was added to the reaction mixture at the same temperature, and then the mixture was stirred for 5 minutes at ambient temperature. The ethyl acetate layer was separated, and the aqueous layer was further extracted with ethyl acetate. The ethyl acetate layers were combined and water (50 ml.) was added thereto. The mixture was adjusted to pH 7.5 with sodium bicarbonate, and the aqueous layer was separated. Ethyl acetate (40 ml.) was added to the aqueous layer, and the mixture was adjusted to pH 2.5 with 10% hydrochloric acid with stirring and ice-cooling. The ethyl acetate layer was separated, and the aqueous layer was further extracted twice with ethyl acetate (30 ml.). The ethyl acetate layers were combined, washed with an aqueous solution of sodium chloride and treated with activated charcoal. The solvent was distilled off to give 7-[2-methoxyimino-2-{2-2,2,2-trifluoroacetamido)-1,3-thiazol-4-yl}acetamido]cephalosporanic acid (syn isomer) (3.05 g.), mp 205° C. (dec.).

1. temperaturecooling
2. distillationdistilled off
3. additionTo the residue were added dry ethyl acetate (10 ml.)
4. temperatureice-cooling
5. stirringThe mixture was stirred for 40 minutes at the same temperature
6. customto give clear solution
7. stirringwith stirring at ambient temperature
8. stirringafter which the mixture was stirred for 1 hour
9. customto give a clear solution
10. stirringwith stirring at -20° to -25° C.
11. stirringthe resulting mixture was stirred for 2 hours at the same temperature
12. stirringthe mixture was stirred for 5 minutes at ambient temperature
13. customThe ethyl acetate layer was separated
14. extractionthe aqueous layer was further extracted with ethyl acetate
15. additionwater (50 ml.) was added
16. customthe aqueous layer was separated
17. additionEthyl acetate (40 ml.) was added to the aqueous layer
18. stirringwith stirring
19. temperatureice-cooling
20. customThe ethyl acetate layer was separated
21. extractionthe aqueous layer was further extracted twice with ethyl acetate (30 ml.)
22. washwashed with an aqueous solution of sodium chloride
23. additiontreated with activated charcoal
24. distillationThe solvent was distilled off

ORD record

ord-171e93725a7640c1a569fd646a18f58e

Source dataset

uspto-grants-1989_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04871860