摘要
以5-甲氧基-2-萘满酮(II)为原料,经缩合、还原、拆分、去甲基等反应制备了(S)-1,2,3,4-四氢-5-羟基-N-丙基-2-萘胺(I)。就I合成的各歩反应条件进行了优化。其中,(S)-1,2,3,4-四氢-5-羟基-N-丙基-2-萘胺的制备采用D-苹果酸作为拆分剂,甲醇∶丙酮体积比为1∶1作溶剂,收率为45%。改进后目标产物的总收率达到了40%。新合成路线操作简便,反应条件温和,使用的原料和试剂成本都比较低廉,适合工业化生产。目标化合物及中间体的结构经1HNMR、ESI-MS等确证。
(S)-5-hydroxy-N-propyl-1,2,3,4-tetrahydronaphthalen-2-amine(I),the key intermediate of Rotigotine was prepared from 5-methoxy-2-tetralone(II)via condensation,reduction,chiral resolution and demethylation.The reaction conditions were optimized for the synthesis of I.The results showed that(S)-5-hydroxy-N-propyl-1,2,3,4-tetrahydronaphthalen-2-amine was obtained with a yield of 45%,using D-malic acid as separation agent and V(Methanol)∶V(acetone)=1∶1 as solvent.The total yield of this target compound was improved to 40%.The structure of target compound was identified by 1H NMR and ESI-MS.The improved process is facile with relatively convenient operation procedures and suitable for industrial production.
作者
郭安军
韩楠
江金凤
辛学
韩爱艺
李洋
Guo Anjun;Han Nan;Jiang Jinfeng;Xin Xue;Han Aiyi;Li Yang(Research Institute of Chia Tai Tianqing Pharmaceutical Group Limited by Share Ltd,Nanjing210042,China)
出处
《广东化工》
CAS
2019年第14期59-59,43,共2页
Guangdong Chemical Industry
