The invention relates to a preparation method of a
cefixime intermediate, which belongs to the technical field of
drug intermediate synthesis, and comprises the following steps: 1, synthesizing an
oxime ether intermediate by using tert-butyl acetoacetate as an initial
raw material and using a two-step one-pot method; in the second step, a chlorination-cyclization one-pot reaction is adopted, wherein the
oxime ether intermediate reacts with NOCl generated by
hydrochloric acid and tert-
butyl nitrite, and a chlorination product is generated; carrying out cyclization reaction with
thiourea and
triethylamine to obtain an acid intermediate; and 3, in order to avoid
decomposition of the product, respectively pulping the acid intermediates-
dichloromethane, DM-
triethylamine and
triphenylphosphine-
dichloromethane, and mixing and reacting in the microchannel to finally obtain the
cefixime intermediate. The whole synthesis
route avoids strong acid and other raw materials with great environmental
pollution, avoids generation of byproducts, obtains high-yield and high-purity products, and shows better economic advantages.