摘要
己二酸单乙酯经氯代、傅-克反应得6-苯基-6-氧代己酸乙酯,经Dieckmann缩合和选择性催化还原羰基得2-苄基环戊酮,经傅-克反应、再与乙二醇反应得6-[4-[2-(1-氯乙基)-1,3-二氧戊环-2-基]苄基]-1,4-二氧螺[4.4]壬烷,在氧化锌作用下进行1,2-芳基重排得2-[4-[(2-氧代环戊基)甲基]苯基]丙酸,再成盐得洛索洛芬钠,总收率58.9%(以己二酸单乙酯计),纯度99.89%。该路线原料价廉易得、收率稳定、操作简便,适合工业化生产。
Ethyl 6-oxo-6-phenylhexanoate was prepared via chlorination and Friedel-Crafts reaction with adipic acid ethyl monoester as the starting material, then it was subjected to Dieckmann condensation and selective catalytic reduction to give 2-benzyl cyclopentanone, which was followed by Friedel-Crafts reaction and acetal reaction to afford
6-[4-[2-（1-chloroethyl）-1,3-dioxolan-2-yl]benzyl]-1,4-dioxaspiro[4.4]nonane, the latter was subjected to a 1,2-aryl rearrangement in the presence of zinc oxide to prepare 2-[4-[（2-oxocyclopentyl）methyl]phenyl]propanoic acid, after an salification, loxoprofen sodium was obtained with an overall yield of 58.9%（based on adipic acid ethyl monoester） and a purity of 99.89%. This process had the advantages of simple procedures and steady yield, and was suitable for production.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2017年第1期12-15,共4页
Chinese Journal of Pharmaceuticals
关键词
洛索洛芬钠
非甾体抗炎药
1
2-芳基重排
合成
loxoprofen sodium
non-steroidal anti-inflammatory drug
1,2-aryl rearrangement reaction
synthesis
