Eisai Chemical Co., Ltd.

Hirofumi Kuroda

Kimio Hamamura

Masahiko Tsujii

Homare Shinohara

Yoshikazu Furusawa

Katsuhiko Hirota

Masato Kodama

An industrially excellent, novel process for producing cephem compounds which are useful as medicines, particularly, antibiotics and represented by the following formula (III): ##STR1## wherein R.sup.1 means either group represented by the following formula: ##STR2## R.sup.2 denotes a carboxyl group or a carboxyl anion, and R.sup.3 stands for a lower alkyl group, a halogen atom, a lower alkyl group substituted by an aliphatic acyloxy group having 1-6 carbon atoms, or any one of the groups represented by the following formulae: ##STR3## which comprises reacting in water a 3-cephem-4-carboxylate represented by the following formula (I): ##STR4## or a salt thereof with an acid chloride represented by the formula (II), R.sup.1 COCl.

Process for producing cephem compounds in an aqueous medium

Disclosed herein is a purification method of a crude product by column chromatography on silica gel or on a vinyl alcohol copolymer. Methanol-containing n-hexane and/or n-hexane-containing methanol is used as an eluent to elute the crude product, thereby obtaining an intended product with high purity and good yield. The solvents recovered from the effluent can be regenerated without any trouble such as rectification and a great cost by mixing them under stirring and then separating the resulting upper and lower layer from each other. The column used can also be reused again and again by washing with methanol. The separation and purification method is excellent in separation efficiency, operation efficiency and economical efficiency.

Purification method of crude product

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Ibaraki Prefecture, Japan

Hirofumi Kuroda