5-Thia-l-aza-bicyclo 4.2.0 oct

To a solution of 1 equivalent (eq.) of lH-tetrazole-1-acetic acid and 1 eq. of triethylamine in 20 ml of tetrahydrofuran cooled to -20°C was added 1 eq. of pivaloyl chloride. After thirty-minute stirring of the mixture 20 ml of a chloroform solution containing 1 eq. of and 1 eq. of triethylamine was poured into the solution cooled at -10°C during a period of 30 minutes. The resulting mixed solution was stirred for 30 minutes at the same temperature, for 1 hour in an ice-water mixture and for 3 hours at room temperature. Removal of a solvent from the reaction mixture afforded an oily residue, which was dissolved into 15 ml of 10% sodium bicarbonate aqueous solution. The resulting aqueous layer was adjusted to pH 1.0-2.0 with 10% hydrochloric acid, washed with ether and extracted with ethyl acetate. The extract was washed with water, dried over sodium sulfate and concentrated under reduced pressure leaving a residue which was triturated with ethyl acetate to obtain 3-acetoxymethyl-8-oxo-7-(2-tetrazol-l-acetylamino)-5-thia-l-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid. 

Oxo-7-phenylacetylamino-5-thia-l-aza-bicyclo[4.2.0]oct-l-ene-2-carboxylic acid benzhydryl ester Phosphorus pentachloride/pyridine reagent... 

The 8-oxo-7-phenylacetylamino-5-thia-l-aza-bicyclo[4.2.0]oct-l-ene-2-carboxylic acid benzhydryl ester is reacted with phosphorus pentachloride/pyridine reagent in methylene dichloride, and the reaction mixture is thereafter cooled to -35°C and treated with methanol to produce hydrochloride of 7-amino-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester. This hydrochloride is reacted with 4-(3-aminothiophen-2-yl)-5-oxohex-3-enoic acid 3-methylbut-2-enyl ester. Then 7-[2-(2-benzoylamino-thiazol-5-yl)(3-tert-butyl-4,4-dimethylpent-2-enoxycarbonyl)-pent-2-enoylamino]-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid synthesized is reacted with aluminum chloride in anisole and diluted hydrochloric acid and then with dimethylmalonate to give 5-thia-l-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid, 7-(((2Z)-2-(2-amino-4-thiazolyl)-4-carboxy-l-oxo-2-butenyl)amino)-8-oxo-, (6R,7R)- (Ceftibuten). 

Sulfon (l-Nitro-cyclopentyl)-phenyl-E19a, 409 (H S02-R) 5-Thia-l-aza-bicyclo[4.2.0]oct-2-en ... 

The data from the IR-LD analysis of cephalosporins, that is, cephalexin, 8-(2-amino-2-phenyl-acetyl)amino-4-methyl-7-oxo-2-thia-6-azabicyclo [4.2.0] oct-4-ene-5-carboxylic acid cephalotin, ((6i ,7R)-3-(acetoxymethyl)-8-oxo-7-(2-(thiophen-2-yl)acetamido)-5-thia-l-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic... 

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