2 - (2 - benzyloxycarbonyl-amino thiazole -4 - yl) -5 - (3 - methyl -2 - butene oxide carbonyl) -2 - E acid synthesis.docVIP

 PAGE \* MERGEFORMAT 22 2 - (2 - benzyloxycarbonyl-amino thiazole -4 - yl) -5 - (3 - methyl -2 - butene oxide carbonyl) -2 - E acid synthesis Author: FENG Ze Wang Cheng-Hui Xin-Qi Zhao 【Abstract】 Ceftibuten the key intermediate 2 - (2 - benzyloxycarbonyl-amino thiazole -4 - yl) -5 - (3 - methyl -2 - butene oxide carbonyl) -2 - E acid (1 ) synthesis process was studied. Domestic use readily available (2 - amino-thiazole -4 - yl) acetate (2) as the starting material, through amino protection, Michael addition - elimination and selective esterification of three-step reaction of the target compounds 1, total yield is 63.0%. The simple process, low production costs, suitable for industrial production. Keywords: 2 - (2 - benzyloxycarbonyl-amino thiazole -4 - yl) -5 - (3 - methyl -2 - butene oxide carbonyl) -2 - E acid; intermediate; ceftibuten; Synthetic ABSTRACT 2 - (2-Benzyloxycarbonylaminothiazol-4-yl) -5 - (3-methyl-2-butenyloxycarbonyl) pent-2-enoic acid (1), the key intermediate of ceftibuten, was prepared from methyl (2-aminothiazol-4 -yl) acetate which could be easily bought in China through a three-step reaction of amino group protection, Michael addition-elimination and selective esterification with an overall yield of 63.0%. This facile and lower-cost process was suitable for industrial production. KEY WORDS 2 - (2-Benzyloxycarbonylaminothiazol-4-yl) -5 - (3-methyl-2-butenyloxycarbonyl) pent-2-enoic acid; Intermediate; Ceftibuten; Synthesis Ceftibuten (ceftibuten, structure see Figure 1) is Japan’s Shionogi has developed successful new third-generation broad-spectrum oral cephalosporins, including Japan, is now widely available around the world. The product and have a broad spectrum antibacterial, anti-bacterial activity of strong and high bioavailability, but also has the right β-lactamases of the unique properties of highly stable [1,2], by the state as “15” the key development during the period species. Ceftibu