Hydrochloric Acid → Diphenylmethyl 7beta-amino-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylate

Temperatur

-10 °C

Pyridine (1.3 ml) was added to a suspension of phosphorus pentachloride (3.37 g) in dichloromethane (47.6 ml) at −10° C., and the mixture was stirred at between −15 to −5° C. for 30 minutes. Diphenylmethyl 7β-phenylacetamido-3-[(1-tritylpyrazol-4-yl)methylthio]-3-cephem-4-carboxylate (6.8 g) was added to the above mixture at −10° C. and the reaction mixture was stirred under ice-cooling for 1 hour. Then, methanol (5.2 ml) was added to the reaction mixture at −20° C. and the resulting solution was stirred under ice-cooling for 1 hour. Water (40 ml) was added to the above mixture under ice-cooling, and stirred for 30 minutes at the same temperature. The aqueous layer was separated and the dichloromethane layer was reextracted with 1 mol hydrochloric acid (30 ml). The aqueous layer and 1 mol hydrochloric acid layer were combined ethyl acetate (50 ml) was added to the aqueous layer and then the mixture was adjusted to pH 3.5 with 30% aqueous sodium hydroxide under stirring. The organic layer was separated, washed with brine (20 ml) and dried over magnesium sulfate. The solvent was distilled off and the residue was pulverized with IPE (50 ml), collected by filtration, washed with IPE (20 ml) and dried over phosphorus pentoxide to give powder of diphenylmethyl 7β-amino-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylate (2.1 g).

1. stirringthe reaction mixture was stirred under ice-
2. temperaturecooling for 1 hour
3. stirringthe resulting solution was stirred under ice-
4. temperaturecooling for 1 hour
5. temperaturecooling
6. stirringstirred for 30 minutes at the same temperature
7. customThe aqueous layer was separated
8. additionwas added to the aqueous layer
9. stirringunder stirring
10. customThe organic layer was separated
11. washwashed with brine (20 ml)
12. dry with materialdried over magnesium sulfate
13. distillationThe solvent was distilled off
14. filtrationcollected by filtration
15. washwashed with IPE (20 ml)
16. dry with materialdried over phosphorus pentoxide

ORD-Eintrag

ord-ec3cd8e5137f4939b98040fabbdad0df

Quelldatensatz

uspto-grants-2002_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06468995B1