An Improved Synthesis of (Z)-2-(5-Amino-1, 2, 4-thiadiazol-3-yl)-2- (Ethoxyimino) Acetic Acid
Songqing Wang, Yi Yao, Kai Chen, Zhujun Fang, Lexian Tong and Weihui ZhongAffiliation:
Key Laboratory of Pharmaceutical Engineering of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, P.R. China.
AbstractAn improved synthetic route of (Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(ethoxyimino)acetic acid (2a), an important intermediate for the preparation of Ceftaroline, from N-(3-aminoisoxazol-5-yl)acetamide (8) in total yield of 47% has been developed. The key intermediate (Z)-N-(3-(2-acetamido-1-(ethoxyimino)-2-oxoethyl)-1,2,4-thiadiazol-5-yl)pivalamide (12a) could easily isolated from (Z/E)-N-(3-(2-acetamido-1-(ethoxyimino)-2-oxoethyl)-1,2,4 -thiadiazol-5-yl)pivalamide. The title compound 2a could be obtained from the hydrolysis of 12a with yield of 83%, and its structure was comfirmed by X-ray single crystal diffraction analysis. Moreover, (E)- and (Z)-N-(3-(2-acetamido-1-(ethoxyimino)-2 -oxoethyl)-1,2,4-thiadiazol-5-yl)pivalamide were prepared respectively from the etherification of oxime hydroxyl group under different conditions. This improved procedure has many appealing attributes such as convenient separation, good yields, and easy access to large scale.
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