合成路线1

The reaction of ethyl acetoacetate (I) with NaNO2 in acetic acid-water gives ethyl 2-(hydroxyimino)-3-oxobutyrate (II), which is cyclized with thiourea (III) by means of SO2Cl2 in methylene chloride yielding ethyl 2-(2-aminothiazol-4-yl)-2-(hydroxyimino)acetate (IV). The treatment of (IV) with trityl chloride (V) and triethylamine in DMF affords ethyl 2-(hydroxyimino)-2-(2-tritylaminothiazol-4-yl)acetate (VI), which by condensation with tert-butyl 2-bromo-2-methylpropionate (VII) by means of K2CO3 in DMSO is converted into ethyl 2-(2-tert-butoxycarbonyl-2-propyloxymino)-2-(2-tritylaminothiazol-4-yl)acetate (VIII). The hydrolysis of (VIII) with NaOH in refluxing methanol gives 2-(2-tert-butoxycarbonyl-2-propyloxyimino)-2-(2-tritylaminothiazol-4-yl)acetic acid (IX), which by condensation with tert-butyl 7-aminocephalosporanate (X) by means of 1-hydroxybenzotriazole and dicyclohexylcarbodiimide in DMF yields tert-butyl 7-[2-(2-tert-butoxycarbonyl-2-propyloxyimino)-2-(2-tritylaminothiazol-4-yl)acetamido]cephalosporanate (XI). The hydrolysis of (XI) with trifluoroacetic acid in anisole affords 7-[2-(2-aminothiazol-4-yl)-2-(2-carboxy-2-propyloxyimino)acetamido]cephalosporanic acid (XII), which is finally treated with pyridine (A) and NaI.