高校化学工程学报2024，Vol.38Issue(3)：468-474,7.DOI:10.3969/j.issn.1003-9015.2024.00.005
左氧氟沙星杂质N的全合成工艺
Total synthesis of levofloxacin impurity N
摘要
Abstract
The compound((S)-(-)-2,3-dihydro-3-methyl-9,10-bis(4-methyl-1-piperazinyl)-7-oxo-7H-pyridino[1,2,3-de][1,4]benzoxazin-6-carboxylic acid)is the impurity N of the antibacterial drug levofloxacin,which is used as the reference substance during the preparation of levofloxacin and hard to synthesize.A novel total synthesis of levofloxacin impurity N(6)was proposed.The intermediate of levofloxacin((S)-(-)-2,3-dihydro-3-methyl-9,10-difluoro-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylate ethyl ester)(1)was used to introduce 8-NO2,and the compound(3)was obtained by nucleophilic substitution of N-methyl piperazine.The compound(6)was obtained by hydrolyzing under the action of sodium hydroxide,reducing with iron powder/ammonium chloride,and diazotizing to remove 8-NH2.The raw materials of the synthesis process are easily available,reaction conditions are temperate,and the levofloxacin impurity N is obtained with the overall yield of about 35.8%and can be applied as the reference substance in levofloxacin-related research.关键词
左氧氟沙星/全合成/左氧氟沙星杂质N/重氮化反应Key words
levofloxacin/total synthesis/levofloxacin impurity N/diazotization分类
化学化工引用本文复制引用
王洁利,王凯,罗艳娟,商甜波,陈彩萍,章潮军,沈华良,沈润溥,虞国棋..左氧氟沙星杂质N的全合成工艺[J].高校化学工程学报,2024,38(3):468-474,7.基金项目
国家自然科学基金(22278270). （22278270）
