利奈唑胺注射液中主要降解产物的合成有机化学.pdfVIP

DOI: 10.6023/cjoc201312033 研究简报 有机化学 Chinese Journal of Organic Chemistry NOTE 利奈唑胺注射液中主要降解产物的合成 黄志雄a 桑志培a 曹海彦a 晁若冰a 邓 勇*,a,b (a 四川大学华西药学院 成都 610041) (b 靶向药物及释药系统教育部重点实验室 成都 610041) 摘要 以利奈唑胺为起始原料, 利用 LiOH 选择性水解利奈唑胺的酯键和酰胺键, 得利奈唑胺注射液中的部分水解产 物 N-[(2R)-3-[[3-氟-4-(4-吗啉基)苯基]氨基]-2-羟基丙基]-乙酰胺(2)和完全水解杂质(2S)-1-氨基-3-[[3-氟-4-(4-吗啉基)苯 基]氨基]-2-丙醇(4), 收率分别为 78.3%和 86.6%; 然后将化合物 4 的末端氨基用叔丁氧羰基保护, 经N,O-双乙酰化后用 氨水/ 甲醇脱除 O-乙酰基, 再利用饱和氯化氢乙醚溶液脱除叔丁氧羰基保护基, 得 N-[(2S)-3-氨基-2-羟基丙基]-N-[3-氟 -4-(4-吗啉基)苯基]-乙酰胺(3)盐酸盐, 五步总收率 62.3%. 关键词 噁唑烷酮类抗菌药; 利奈唑胺; 注射液; 降解产物; 杂质; 合成 Synthesis of Major Degradation Products of the Injection of Linezolid Huang, Zhixionga Sang, Zhipeia Cao, Haiyana Chao, Ruobinga Deng, Yong*,a,b a ( Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041) b ( Key Laboratory of Drug Targeting and Drug Delivery System, Chengdu 610041) Abstract The ester bond and amide bond of linezolid were selectively hydrolyzed by using LiOH to afford N-[(2R)-3- [[3-fluoro-4-(4-morpholino)phenyl]amino]-2-hydroxypropyl] acetamide (2) and (2S)-1-amino-3-[[3-fluoro-4-(4-morpholino)- phenyl]-amino]-2-propanol (4) with 78.3% and 86.6% yields respectively, which were the partially hydrolyzed impurity and fully hydrolyzed impurity of the injection of li