Control of crystal habit and size of cefmatilen hydrochloride hydrate with a habit modifier

Control of crystal habit and size of cefmatilen hydrochloride hydrate (1) with a habit modifier is described here. One of the related substances, impurity 2, which has a diphenylmethyl group at the N3-position of the triazolyl group of cefmatilen, acts as a habit modifier. The crystal habit and size of compound I depended upon the amount of impurity 2 in the crystallizing system. Since the amount of impurity 2 can be controlled by the temperature during the addition of AlCl3 to a suspension of compound 3 in the deprotection step, the crystal habit and size can be controlled by the temperature of addition of AlCl3 .The addition of small amounts of hydroxyalkylcelluloses or polyvinyl derivatives to the crystallizing system can also modify the crystal habit and size of compound 1.