| 第 48 卷第 2 期 |  | Vol. 48 No. 2 | | 2018 年 4 月 | Apr 2018 |
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所屬欄目：醫藥及中間體
拉氧頭孢鈉合成工藝的改進(jìn) |
| 何小鵬，黃偉平，李日生
（浙江東邦藥業(yè)有限公司 浙江 臨海 317016） |
| 摘 要：以氧頭孢烯為起始原料，通過(guò)甲氧基化得到甲氧基氧頭孢烯，然后在磺酰氯和三乙胺催化作用下，反應得到（6R，7R）-苯甲酰氨基-3-（1-甲基-5-四氮唑）-硫甲基-7-甲氧基-8-氧代-5-氧雜-1-氮雜二環(huán)［4.2.0］辛-2-烯-2-羧酸二苯甲酯，然后依次在五氯化磷，吡啶和氯化氫作用下去氨基，羧基保護，最后在�；缸饔孟逻M(jìn)行氨基�；腿苊椒ǔ甥}生成拉氧頭孢鈉�？偸章视�30%提高到49%，產(chǎn)物含量在92%以上，產(chǎn)物結構經(jīng)核磁進(jìn)行了表征。 整條路線(xiàn)步驟少，操作簡(jiǎn)單，節約成本，工藝路線(xiàn)綠色環(huán)保，適合工業(yè)化生產(chǎn)。 |
| 關(guān)鍵詞：氧頭孢烯；拉氧頭孢鈉；縮合 |
| 中圖分類(lèi)號：R914 文獻標識碼：A 文章編號：1009-9212（2018）02-0043-04 |
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| An Improved Process for the Synthesis of Latamoxef Disodium |
| HE Xiao-peng, HUANG Wei-ping, LI Ri-sheng
(Zhejiang Dong Bang Pharmaceutical Co., Ltd., Linhai 317016, China) |
| Abstract：In this process, methoxy oxacephem is formed by methoxylation reaction using oxacephem as the starting material. (6R,7R)-Benzamindo-3-(1-methyl-5-tetrazolium) thiomethyl-7-methoxy-8-oxo-5- oxa-1-azabicyclo[4.2.0]Oct-2-ene-2-carboxyylic acid benzhydryl ester was obtained from a series reactions including the catalytic reaction of sulfuryl chloride and trimethylamine, and deprotection of amino and carboxyl under the action of phosphorus pentachloride, pyridine and hydrogen chloride respectively. In the final, under the action of acylase, Latamoxef disodium was obtained by aminoacylation reaction and solvent salt forming reaction. The yield was increased from 30% to 49%. The purity of product was of more than 92%. And the structure of the product was characterized by 1H NMR, 13C NMR. The preparation process was of less steps and simple in operation, low cost, green and environmental friendly, and suitable for industrial production. |
| Key words：oxacephem; Latamoxef disodium; condensation |
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作者簡(jiǎn)介：何小鵬（1974-），男，浙江臺州人，工程師，主要從事藥物合成研究（E-mail：hexiaopeng222@sohu.com）。
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收稿日期：2018-04-03
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