3-cephem derivative crystal

#The present invention relates to a 3-cephem derivative in crystalline form which can be prepared by a novel crystallization method, the 3-cephem derivative being useful as an intermediate or a final product of pharmaceuticals such as cefixime, ceftibuten and cefdinir (Katsuharu SAKAI, “Handbook of Recent Antibiotics”, p.p.83, 85 and 86) which are currently widely used as pharmaceutical antibiotics, and a process for preparing the same.

#Generally employed for crystallizing 3-cephem derivatives are crystallization methods using a combination of a good solvent which is superior in the power of dissolving the substrate and a poor solvent which is inferior in the power of dissolving the substrate.

#However, these conventional crystallization methods have the following defect. The poor solvent partly becomes highly concentrated in the crystallization system when the poor solvent is dispersed in the good solvent, so that an amorphous powder is produced in most cases without formation of crystalline nucleus because of abrupt deposition occurring in the part. In addition, the obtained 3-cephem derivative is very unlikely to have enhanced purity because it generally contains impurities.

#FIG. 1 shows 1H-NMR spectrum of 3-cephem derivative crystals of the invention obtained in Example 1.

#The novel crystallization method of the invention will be described below with reference to the following reference examples and examples to which, however, the invention is not limited.

#Isopropyl alcohol (2000 ml) was placed into a 3 liter-eggplant type flask and was cooled to 3° C. Separately a solution of 120 g of an amorphous powder of p-methoxybenzyl ester of 7-phenylacetamide-3-formyl-3-cephem-4-carboxylic acid [3-formylcephem compound (1)] (88% purity) in 120 ml of dimethylformamide was prepared.

#The dimethylformamide solution was added dropwise to the sufficiently cooled isopropyl alcohol. The mixture was stirred for 1 hour while holding the internal temperature at 5 to 10° C., whereby a powder of 3-formylcephem compound (1) was precipitated. After completion of aging, the precipitate was filtered. After filtration, the obtained particles were washed with 300 ml of isopropyl alcohol at 5° C.