HCID 67832774, compound → HCID 68122657, compound

In Chem Pharm Bull, 36(2), 582-591 (1988), the preparation of 7-amino-3-hydroxy-3-cephem-4-carboxylic acid (IX) is described in which 7-amino-3-exomethylene-cepham-4-carboxylic acid (VII) was ozonized in methanol at -75° C. to yield the corresponding 3-hydroxy-3-cephem compound (VIII) which is further reduced with NaBH4 to yield 83% of (IX). It was also observed that when 7-phenylacetamido-3-methylene-cepham-4-carboxylic acid (X) was ozonized in methylene chloride, the desired 3-hydroxy-3-cephem compound (XI) was not obtained, but when ozonolysis of (X) was carried out in methanol at -65° C. followed by treatment of the reaction mixture with excess of diphenyl diazomethane the ester (XII) was obtained. The above process is illustrated in the following Scheme B: ##STR3## F) U.S. Pat. Nos. 3,917,587, 3,925,372, 4,064,343, 4,060,688 describe the ozonization of the 7-amino or 7-acylamido-3-exomethylene-cepham-4-carboxylic acid esters in solvents like methylene chloride, methanol, ethyl acetate etc., at a temperature range of -80° C. and -50° C. and the resulting ozonide is always decomposed with a reducing agent such as sodium bisulfite, sulphur dioxide and trimethylphosphite to afford the corresponding 3-hydroxy-3-cephem-4-carboxylic acid esters. Also mentioned is the formation of sulfoxide side products, the 3-exomethylene sulfoxide ester and the 3-hydroxy-3-cephem ester. The formation of the sulfoxides is said to occur as a result of over oxidation in the ozonolysis reaction.

ORD record

ord-b8592b404712453086d598e802506de6

Source dataset

uspto-grants-1998_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05750683