The invention relates to a preparation method of
cefoxitin. The method comprises the following steps: adding a
solvent A into a compound
aqueous solution with the structure shown in the formula (IV), adding N,N'-dibenzylethylenediamine diacetate or
aqueous solution thereof, filtering to obtain a compound with an
intermediate structure shown in the formula (III); adding the compound with the
intermediate structure shown in the formula (III) into
acetone or
tetrahydrofuran, adding chloriosulfonyl
isocyanate to react, and hydrolyzing; adding acetic
ether, filtering, extracting, decoloring,
salting out, and filtering to obtain a compound with an
intermediate structure shown in the formula (II); adding the compound with the intermediate structure shown in the formula (II) into an
organic solvent B, adding
organic acid to dissolve, adding a
methanol solution with
sodium methoxide and tert-butyl
hypochlorite to perform
methylation reaction, adding
sodium pyrosulfite and
acetic acid for neutralizing, adding water for extracting, acidifying water phase, filtering to obtain
cefoxitin. According to the preparation method, deacetyled
cefoxitin always exists in a mode of
sodium salt or amine salt, so that the condensation
side reaction easily caused by low pH can be avoided, and the product quality and yield can be well controlled.