4-乙酰氨基-3-(3-戊氧基)苯甲酸的合成  

Synthesis of 4-(N-acetylamino)-3-(3-pentyloxy) benzoic acid

作　　者：贺丽敏[1] 胡艾希[2] 

机构地区：[1]广东药学院药科学院,广东广州510006 [2]湖南大学化学化工学院,湖南长沙410082

出　　处：《广东药学院学报》2010年第4期362-364,共3页Academic Journal of Guangdong College of Pharmacy

基　　金：国家教育部博士点专项基金(20040532002)

摘　　要：目的改进可能具有抗流感病毒活性的化合物4-乙酰氨基-3-（3-戊氧基）苯甲酸的合成方法。方法以间羟基苯甲酸为原料,经酯化、硝化、催化氢化、烷基化、酰化及水解6步反应制备4-乙酰氨基-3-（3-戊氧基）苯甲酸。结果甲酯化收率86.9%;硝化反应采用硝酸/乙酸酐混酸作硝化试剂,收率23.5%;硝基还原用质量分数5%钯-碳作催化剂催化氢化,收率95.8%;烷基化反应中先使酚羟基与氢化钠成盐,然后再与3-溴戊烷反应,收率44.4%;酰化反应用DMAP作催化剂,采用向碎冰上倾倒反应液使产物析出的后处理方法,收率82.8%;酯水解中改用丙酮做溶剂,反应时间由15h缩短至4h,收率86.8%。各中间体和目标化合物结构经1H-NMR确证。结论改进的反应条件缩短了反应时间,简化了后处理步骤,为今后该类流感药物的研发奠定了基础。Objective To improve the synthetical method of 4-（N-acetylamino）-3-（3-pentyloxy）benzoic acid,which has been reported with certain anti-influenza virus activity. Methods 4-（N-acetylamino）-3-（3-pentyloxy）benzoic acid was prepared by six-step reaction of esterification,nitration,catalytic hydrogenation,alkylation,acylation,and hydrolysis with m-hydroxybenzoic acid as raw material. Results The yield of esterification was 86.9%; Mixed acid of nitric acid and acetic anhydride as nitration reagent,the yield of nitration was 23.5%; 5% Pd-C as hydrogenation catalyst,the yield was 95.8%; In the alkylation,phenolic hydroxyl formed salt with sodium hydride,then reacted with 3-bromo pentane,and the yield was 44.4 %; DMAP as catalyst,the post-processing steps were simplified with the method of pouring the reaction solution into ice,the yield was 82.8%; The reaction time was shortened from the 15 h to 4 h with acetone as solvent in the reaction of hydrolysis,and the yield was 86.8%. The structures of all intermediates and the target compound were confirmed by 1HNMR. Conclusion The improved reaction conditions shortened the reaction time,simplified the post-processing steps,and established the foundation for future development of this type of influenza drugs.

关 键 词：流感神经氨酸酶抑制剂 4-乙酰氨基-3-(3-戊氧基)苯甲酸 间羟基苯甲酸 合成 

分 类 号：R914[医药卫生—药物化学]