6-(4-(1-羧乙基)苯基)-5-氧代己酸的合成工艺改进研究
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摘要
目的对6-(4-(1-羧乙基)苯基)-5-氧代己酸的合成工艺条件进行优化。方法以洛索洛芬为原料,通过取代、氧化、水解、再氧化反应得到目标化合物6-(4-(1-羧乙基)苯基)-5-氧代己酸。结果合成了目标化合物,经MS、1H-NMR确证了结构,质量分数为97%,本合成工艺的总收率为21.2%。结论合成了一种洛索洛芬的杂质,可作为洛索洛芬原料药质量控制的杂质对照品。
Objective To optimize the synthetic process of 6-(4-(1-carboxyethyl)phenyl)-5-oxohexanoic acid. MethodsLoxoprofen was used as starting material to obtain the target product through substitution, oxidation, hydrolysis, and oxidation reaction. Results The target compound was synthesized and characterized by MS and 1H-NMR. The purity was 97%, and the total yield of this route was 21.2%. Conclusion The synthetic compounds can be used as the reference substance of the impurities in the quality control of loxoprofen.
Objective To optimize the synthetic process of 6-(4-(1-carboxyethyl)phenyl)-5-oxohexanoic acid. MethodsLoxoprofen was used as starting material to obtain the target product through substitution, oxidation, hydrolysis, and oxidation reaction. Results The target compound was synthesized and characterized by MS and 1H-NMR. The purity was 97%, and the total yield of this route was 21.2%. Conclusion The synthetic compounds can be used as the reference substance of the impurities in the quality control of loxoprofen.
引文
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[2]郭锦林,章映娴,王文清.口服洛索洛芬致眩晕1例[J].中南药学,2011,11(10):800.
[3]周淑琴.新型非甾体抗炎药洛索洛芬钠的研究进展[J].上海医药,2008,29(10):468-469.
[4]刘彦彬,蔡亚辉,吴艳华,等.一种洛索洛芬钠开环杂质的制备方法[P].CN:107353195,2017-11-17.
[5]唐文生,潘丽坤,孙平华,等.非甾体抗炎药洛索洛芬钠的合成改进[J].中国药物化学杂志,2002,12(5):46-48.
[6]Wu Y K,Li Y,Wu Y L.Tandem hemiketal formationintramolecular Friedel-Crafts alkylation:a facile route to hetero-atom-substituted benzo-fused bicyclo[3.3.1]nonanes[J].Helv Chim Acta,2001,84(1):163-171.
[7]Tadashi H.Surface photoreactions of 2-benzoylcyclpentanones:silical gel surface as a possible field bringing out the latent reactivity of dispersed molecules[J].J Phys Org Chem,1996,9(10):677-682.
[8]Lin C P,Gitsov I.Preparation and characterization of novel amphiphilic hydrogels with covalently attached drugs and fluorescent markers[J].Macromolecules,2010,43(23):10017-10030.