At room temperature (15-25C), 171g of sodium isocaproate (1.03 mol) was dissolved in 900mL of water and 200mL of acetone, and 300g of cefepime sulfate (0.52 mol, weight by weight in anhydrous) was added in batches with effective stirring to form a well-flowing slurry system. 1600mL of acetone and an appropriate amount of activated charcoal were added after 10 minutes and stirred for 30 minutes. The solid was separated by centrifugation or diafiltration. The filter cake was washed with 500 mL of a mixed acetone-water 2:1 (v/v) solution and the filtrates were combined. 18% HCl was added to the filtrate with stirring to pH 1.0 to 1.5. 8 L of acetone was then added over 1 hr. The system was cooled down again to 5 to 10C and stirring was continued for 1 hr. Filter extraction. The filter cake was washed with acetone and dried under vacuum at 40C to give about 270 g of white crystalline powder. Purity 99.7%, water content 3.8% (K-F method), acetone residue 0.25%. The product is cefepime dichlorohydrate monohydrate, i.e. cefepime hydrochloride. All quality indicators meet the requirements of the U.S. Pharmacopeia.
