反应详情

The silylated product and the mixed anhydride are then combined in the cold to form an intermediate protected cephalexin (V) that is not isolated. This reaction is illustrated below: ##STR3## The product is then hydrolyzed to remove the silyl groups, forming cephalexin hydrochloride in solution. The hydrochloride is neutralized with a base in aqueous methanol to form the desired product, cephalexin monohydrate which has the formula (VI): ##STR4## The above process always gives incomplete reaction of 7-ADCA to cephalexin. It has a yield that is lower than desired, e.g., in the range of about 70-75%. Low yields add to the cost of producing the product. The final product is sometimes contaminated with the 7-ADCA starting material. Attempts to improve the purity of the product by altering reaction conditions, such as time, temperature, concentration of reactants, ratios of starting materials and the like have had little effect on purity. Prevention of coprecipitation of 7-ADCA with the product is difficult because 7-ADCA tends to form as an amorphous material along with the crystalline product, if the pH of a solution of both is simply raised to the isoelectric point of cephalexin. A better crystallization is done by an awkward "simultaneous" method by feeding both the acidic product solution and a caustic solution into a reservoir at a pH of 6.5-7.0 to prevent coprecipitation of the 7-ADCA. This process is cumbersome at best.