- Synthesis of Cefbuperazone sodium
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Cefbuperazone sodium (CAS NO.: ), with its other name of 5-Thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid, 7-(2-((2,3-dioxo-4-ethyl-1-piperazinyl)formamido)-3-hydroxybutyramido)-7-methoxy-3-(((1-methyl-1H-tetrazol-5-yl)thio)methyl)-8-oxo-, monosodium salt, (6R-(6-alpha,7-alpha,7(2R*,3S*)))-, could be produced through many synthetic methods.
Following is one of the synthesis routes:
Firstly, 4-ethyl-2,3-dioxo-1-piperazinecarbonyl chloride (I) could be condensed with threonine (II) in methylene chloride to produce alpha-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-beta-hydroxybutyric acid (III), which is then condensed with diphenylmethyl 7-beta-amino-3-[(1-methyltetrazol-5-yl)thiometnyl)-Delta3-cephem-4-carboxylate (IV) in the presence of ethyl chloroformate and N-methyl morpholine affording diphenylmethyl 7-beta-[alpha-(4-ethyl-2,3-dioxo-1-piperazi-necarboxamido)-beta-hydroxybutyramido]-3-(11-methyltetrazol-5-yl)thiomethyl]-Delta3-cephem-4-carboxylate (V). Next, the methoxylation of (V) with lithium methoxide-methylene chloride THF affords diphenyl methyl 7-beta-[alpha-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-beta-hydroxybutyramido]-7-alpha-methoxy-3-[(1-methyltetrazol-5-yl)thiamethyl-Delta3-cephem-4-carboxylate (VI), which is finally hydrolyzed with trifluoroacetic acid, and treated with NaHCO3 to obtain the sodium salt.
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