The condensation of (II) with the substituted phenylacetic acid (X) by means of ethyl chlorocarbonate gives the cephalosporin (XI), which is then cyclized by means of NaH in ethanol.
By condensation of alpha-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)-p-hydroxyphenylacetic acid (I) with 7-amino-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylic acid (II) by means of ethyl chlorocarbonate and N,O-bis(trimethylsilyl)acetamide in acetonitrile.
The condensation of N-(1-methoxycarbonyl-1-propen-2-yl)-alpha-amino-p-hydroxyphenylacetic sodium salt (III) with 7-amino-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylic acid (II) by means of ethyl chlorocarbonate and N,O-bis(trimethylsilyl)acetamide (A) in acetonitrile gives 7-(alpha-amino-p-hydroxy-phenylacetamido)-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylic acid (IV), which is then condensed with 4-ethyl-2,3-dioxopiperazino-1-carbonyl chloride (V) by means of K2CO3 in ethyl acetate water.
The condensation of alpha-(4-ethyl-2,3-dioxo-1-piperazinocarbonylamino)-p-hydroxyphenylacetic acid (I) with 7-amino-3-acetoxymethyl-3-cephem-4-carboxylic acid (VI) by means of ethyl chlorocarbonate and N,O-bis(trimethylsilyl)acetamide (A) gives the 3-acetoxymethyl derivate (VII), which is then condensed with 1-methyl-5-mercapto-1H-tetrazole (VIII) by means of NaHCO3 in a phosphate buffer.
The condensation of acetoxymethyl derivative (VI) with N-(1-methoxycarbonyl-1-propen-2-yl)-alpha-amino-p-hydroxyphenylacetic sodium salt (III) by means of ethyl chlorocarbonate and N,O-bis(trimethylsilyl)acetamide (A) gives 7-(alpha-amino-p-hydroxyphenylacetamido)-3-acetoxymethyl-3-cephem-4-carboxylic acid (IX), which is then condensed with acyl chloride (V) by means of K2CO3 in ethyl acetate water to afford (VII), which is then condensed with 1-methyl-5-mercapto-1H-tetrazole (VIII) by means of NaHCO3 in a phosphate buffer.