头孢西酮中间体的合成研究
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摘要
以3,5-二氯吡啶为原料,经4步反应制得头孢西酮中间体3,5-二氯-4-吡啶酮乙酸。原料经硝化、还原、重氮化水解、缩合反应制得产物。对各步单元反应进行了条件优化,得到了最优反应条件,4步反应收率为57.6%,HPLC含量为97.5%。反应产物结构经~1HNMR和~(13)CNMR确证,整个合成工艺简单、收率高,具有很好的工业应用前景。
The target compound 3,5-dichloropyridine acetic acid is an important intermediate of Cefasidone which can be prepared from 3,5-dichloropyridine via nitrification,reduction,diazo hydrolysis and condensation.The optimum reaction conditions were obtained,the overall yield of four steps reaction was 57. 6% and the purity of final product was 97. 5%.The structure was confirmed by1 HNMR and13 CNMR.The smooth synthetic process with high yield made it suitable for industrial application.
The target compound 3,5-dichloropyridine acetic acid is an important intermediate of Cefasidone which can be prepared from 3,5-dichloropyridine via nitrification,reduction,diazo hydrolysis and condensation.The optimum reaction conditions were obtained,the overall yield of four steps reaction was 57. 6% and the purity of final product was 97. 5%.The structure was confirmed by1 HNMR and13 CNMR.The smooth synthetic process with high yield made it suitable for industrial application.
引文
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[2]DINGELDEIN E,WAHIG H,BERGMANN R.Cefazedone,a new semisynthetic cephalosporin derivative:in vitro and in vivo antibacterial activities[J].Curr.Chemother.,Proc.Int.Congr.Chemother.,1978,2(10):832-834.
[3]ROLF W R,ROLF B.Pyridone-acetic acid derivative:US,4 243 810A[P].1981-01-06.
[4]杨明波,汪令,贾爱琼,等.3,5-二氯-4-吡啶酮乙酸合成工艺优化[J].中国抗生素杂志,2017,42(5):360-362.
[5]张环宇,曲有乐,周淑晶.3,5-二氯-4-吡啶酮乙酸的合成[J].黑龙江医药科学,2006,29(1):41-42.
[6]FENTON G,MORLEY A D,PALFREYMAN M N,et al.N-(Hetero)aryl-3,4-(cyclo)alkoxybenzamides and analogs useful as tumor necrosis factor and c-AMP phosphodiesterase inhibitors:US,5 935 978[P].1999-10-10.
[7]杨绿,闫海英,陈新志.4-羟基吡啶合成研究[J].化学世界,2003,10(10):538-540.
[8]熊振湖,费学宁.4-羟基吡啶合成方法的改进[J].化学研究,2001,12(4):37-38.
[9]UPADYSHEVA A V,GRIGOR N D,ZNAMENSKAYA A P.Intramolecular rearrangement of bicyclic 2,2-disubstituted 4-oxo-1,2,3,4-tetrahydropyrimidines in the presence of polyphosphoric acid[J].Khim.Geterotsikl.,1977,11:1 549-1 553.
[10]COLLIER S J.Product subclass 10:N-haloenamines[J].Sci.Synt.,2007,33:487-492.