Practical Large-Scale Synthesis of Cefmatilen, A New Cephalosporin Antibiotic

• DOI: 10.1021/op049920i
• Publication Date: 2004-09-17T04:22:08Z
• Authors: Tatsuya Kobayashi; Yoshiyuki Masui; Yoshihisa Goto; Yoji Kitaura; Taiku Mizutani; Isao Matsumura; Yoshihide Sugata; Yutaka Ide; Masami Takayama; Hisanori Takahashi; Akira Okuyama
• Keywords: Cephalosporin Antibiotic; Hydrochloride; Cephalosporin C

A practical large-scale process for the synthesis of cefmatilen hydrochloride hydrate (1), a new oral cephalosporin antibiotic, is described. Several impurities are isolated from bulk drug and identified. Side reactions discussed in order to prevent them. The conditions were optimized control formation impurities. amenable multikilogram-scale preparation. kilograms compound 1 clinical trials successfully prepared by this three starting materials (7-aminocephem 4, triethylammonium acetate 5, triazole 7) on pilot scale overall yields 61−65% (10−14% higher than those previous process).