Phosphorus oxychloride → HCID 131712382, compound

Temperature

40 °C

A mixture of N,N-dimethylformamide (10 ml.) and phosphorus oxychloride (0.507 g.) was warmed at 40° C. for 30 minutes and subsequently cooled to -10° C. and thereto was added 2-[N-(2-hydroxy-5-chlorophenyl)carbamoylmethoxyimino]-2-(2-formamidothiazol-4-yl)acetic acid (syn isomer) (1.00 g.). The resulting mixture was stirred at -10° to -5° C. for 50 minutes. On the other hand, to a solution of trimethylsilylacetamide (3.60 g.) in methylene chloride (15 ml.) was added 7-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (1.003 g.). To this solution was added the stirred mixture obtained above at -25° C. followed by stirring at -20° to -10° C. for 2 hours. After concentration of the reaction mixture, to the residue were added a saturated aqueous solution of sodium bicarbonate (25 ml.) and water (50 ml.). The resulting mixture was washed with ethyl acetate and thereto was added ethyl acetate (100 ml.). The mixture was adjusted to pH 2 with 10% hydrochloric acid and extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate, treated with activated charcoal and then concentrated. The residue was triturated with diethyl ether and the precipitates were collected by filtration and then washed with diethyl ether to give a powder (1.0 g.), which was dissolved in a small amount of a mixture of acetone and ethyl acetate. This solution was washed with water twice, dried over magnesium sulfate and then concentrate to a small volume. To the concentrate was added diethyl ether followed by stirring at room temperature overnight. The precipitates were collected by filtration, washed with diethyl ether and dried to give the title compound (0.63 g.).

1. temperaturesubsequently cooled to -10° C.
2. additionTo this solution was added the stirred mixture
3. customobtained above at -25° C.
4. stirringby stirring at -20° to -10° C. for 2 hours
5. washThe resulting mixture was washed with ethyl acetate
6. additionwas added ethyl acetate (100 ml.)
7. extractionextracted with ethyl acetate
8. washThe extract was washed with water
9. dry with materialdried over magnesium sulfate
10. additiontreated with activated charcoal
11. concentrationconcentrated
12. customThe residue was triturated with diethyl ether
13. filtrationthe precipitates were collected by filtration
14. washwashed with diethyl ether
15. customto give a powder (1.0 g.), which
16. washThis solution was washed with water twice
17. dry with materialdried over magnesium sulfate
18. concentrationconcentrate to a small volume
19. additionTo the concentrate was added diethyl ether
20. stirringby stirring at room temperature overnight
21. filtrationThe precipitates were collected by filtration
22. washwashed with diethyl ether
23. customdried

ORD record

ord-aed5730d84334cbda38c904b600998f3

Source dataset

uspto-grants-1988_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04782158