A Z-isomer (4) of 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(methoxyimino)acetic acid, which is the common acyl moiety of clinically useful cephem antibiotics, has been prepared from the aminoisoxazoles through the skeletal rearrangement in several routes. Reaction of 3-amino-5-methoxyisoxazole (7) with alkoxycarbonyl isothiocyanates gave methyl 2-(5-alkoxycarbonylamino-1,2,4-thiadiazol-3-yl)acetates (8), which were converted into the target compound 4 through the reaction of the corresponding keto ester with O-methylhydroxylamime. Compound 4 was prepared similarly from 3-aminoisoxazole (10). Also, O-methylation of 2-hydroxyimino-2-(5-methoxycarbonylamino-1,2,4-thiazol-3-yl)acetate (15) with methyl iodide or dimethyl sulfate in the presence of barium oxide and barium hydroxide octahydrate was found to afford exclusively the desired Z-isomer (14a) of methyl 2-(5-methoxycarbonylamino-1,2,4-thiadiazol-3-yl)-2-(methoxyimino)acetate, which was led to 4.

中文翻译：

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(Z)-2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-甲氧基亚氨基乙酸的实际制备：第四代头孢菌素抗生素的侧链

2-(5-氨基-1,2,4-噻二唑-3-基)-2-(甲氧基亚氨基)乙酸的 Z-异构体 (4)，它是临床上有用的头孢烯抗生素的常见酰基部分，已被由氨基异恶唑通过几种途径的骨架重排制备。3-氨基-5-甲氧基异恶唑 (7) 与烷氧基羰基异硫氰酸酯反应生成 2-(5-烷氧基羰基氨基-1,2,4-噻二唑-3-基)乙酸甲酯 (8)，通过以下反应转化为目标化合物 4相应的酮酯与 O-甲基羟胺的反应。化合物4类似地由3-氨基异恶唑(10)制备。此外，2-羟基亚氨基-2-(5-甲氧基羰基氨基-1,2,