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2-甲氧基-5-氟苯甲酸(2)经甲基化得2-甲基-3-氟-6-甲氧基苯甲酸(3)和2的混合物,不经分离直接酯化和定向水解后分离纯化得2和2-甲基-3-氟-6-甲氧基苯甲酸苯酯(4),4经脱甲基、邻位硝化及氢化还原得2-甲基-3-氟-5-氨基-6-羟基苯甲酸苯酯(8),8的羟基和氨基同时经苄基保护,反应结束后通过缓慢降温便可析出eravacycline的关键中间体2-甲基-3-氟-5-二苄基氨基-6-苄氧基苯甲酸苯酯(1),避免使用柱色谱纯化。总收率52.8%(以2计)。
Methylation of 2-methoxy-5-fluorobenzoic acid (2) gives a mixture of 2-methyl-3-fluoro-6-methoxybenzoic acid (3) and 2 which is directly esterified without isolation and After the directional hydrolysis, 2 and 2-methyl-3-fluoro-6-methoxybenzoate (4) were isolated and purified. 4 was demethylated, ortho nitrated and hydrogenated to give 2-methyl- Fluoro-5-amino-6-hydroxy-benzoic acid phenyl ester (8), 8 hydroxy and amino simultaneously protected by benzyl, by the end of the reaction after cooling down precipitated the key intermediate of eravacycline 2-methyl-3-fluoro -5-dibenzylamino-6-benzyloxybenzoic acid phenyl ester (1), avoiding purification by column chromatography. The total yield of 52.8% (2).