合成路线1

This compound can be prepared by the route shown in scheme: Reaction of chlorodifluoromethane (Freon 22) with ethyl thioglycolate (II) in the presence of ethanolic sodium ethoxide gives ethyl 2-(difluoro-methylthio)acetate (III), which is hydrolyzed with aqueous potassium hydroxide to yield 2-(difluoromethylthio)acetic acid (IV). Substitution of diphenylmethyl-7alpha-benzamido-3-chloromethyl-1-oxa-3-cephem-4-carboxylate (V), an important intermediate for production of latamoxef, with 1-(2-hydroxyethyl)-1H-tetrazole-5-thiol (VI) in the presence of sodium methoxide, followed by protection of the hydroxyl group by means of p-methylbenzyl chlorocarbonate (VII) and pyridine, gives diphenylmethyl 7alpha-benzamido-3-[[1-[2-(p-methylbenzyloxycarbonyloxy)ethyl-1H-tetrazol-5-yl]thiomethyl]-1-oxa-3-cephem-4-carboxylate (VIII). Methoxylation of (VIII) with tert-butylhypochlorite and lithium methoxide, followed by the conventional side-chain cleavage with phosphorus pentachloride pyridine methanol, affords diphenylmethyl 7beta-amino-7alpha-methoxy-3-[[1-[2-(p-methylbenzyloxycarbonyloxy)ethyl]-1H-tetrazol-5-yl]thiomethyl]-1-oxa-3-cephem-4-carboxylate (X). This amine (IX) is condensed with the acid (IV) by means of phosphoryl chloride and pyridine fo yield diphenyl-methyl 7beta[2-(dfluoromelhylthio)acetamido]-7alpha-methoxy-3-[[1-[2-(p-methylbenzyloxycarbonyloxy)ethyl]-1H-tetrazol-5 yl)thiomethyl]-1-oxa-3-cephem 4-carboxylate (X), which undergoes deprotection with stannic chloride and anisole, neutralization with aqueous sodium bicarbonate and lyophilization giving the sodium salt (XI).