本文關(guān)鍵詞： eravacycline 四環(huán)素 中間體 合成　出處：《中國醫(yī)藥工業(yè)雜志》2017年04期 　論文類型：期刊論文

【摘要】：2-甲氧基-5-氟苯甲酸(2)經(jīng)甲基化得2-甲基-3-氟-6-甲氧基苯甲酸(3)和2的混合物,不經(jīng)分離直接酯化和定向水解后分離純化得2和2-甲基-3-氟-6-甲氧基苯甲酸苯酯(4),4經(jīng)脫甲基、鄰位硝化及氫化還原得2-甲基-3-氟-5-氨基-6-羥基苯甲酸苯酯(8),8的羥基和氨基同時經(jīng)芐基保護,反應(yīng)結(jié)束后通過緩慢降溫便可析出eravacycline的關(guān)鍵中間體2-甲基-3-氟-5-二芐基氨基-6-芐氧基苯甲酸苯酯(1),避免使用柱色譜純化�？偸章�52.8%(以2計)。
[Abstract]:The mixture of 2-methyl-3-fluoro-6-methoxybenzoic acid and 2 was synthesized by methylation of 2-methoxy-5-fluorobenzoic acid. 2 and 2-methyl-3-fluoro-6-methoxy benzoate benzene ester was purified by direct esterification and directional hydrolysis without separation, and then demethylated from 2 and 2-fluoro-6-methoxy benzoate. The hydroxyl and amino groups of 2-methyl-3-fluoro-5-amino-6-hydroxybenzoate (BBA _ 8) were protected by benzyl group at the same time by nitration and hydrogenation of 2-methyl-3-fluoro-5-amino-6-hydroxybenzoate. At the end of the reaction, the key intermediate of eravacycline can be precipitated by slow cooling, 2-methyl-3-fluoro-5-dibenzyl amino-6-benzoxybenzoate (1). To avoid the use of column chromatography purification. Total yield of 52.8%.
【作者單位】： 中國醫(yī)藥工業(yè)研究總院上海醫(yī)藥工業(yè)研究院創(chuàng)新藥物與制藥工藝國家重點實驗室;
【分類號】：R914.5
【正文快照】： 美國四相制藥公司研發(fā)的eravacycline(TP-434)是首個進入臨床的全合成四環(huán)素[1],目前仍處于Ⅲ期臨床,有望用于治療復雜性腹腔感染。2-甲基-3-氟-5-二芐基氨基-6-芐氧基苯甲酸苯酯(1)是合成eravacycline的關(guān)鍵中間體[2]。目前文獻只報道了1種合成方法:2-甲氧基-5-氟苯甲酸(2)在，

本文編號：1491032