摘要
2,3-二氢苯并呋喃经Vilsmeier-Haack反应、Wittig-Horner缩合和双键还原得到3-(2,3-二氢苯并呋喃-5-基)丙酸乙酯,再经碘催化进行一步双溴代、水解、环合、脱溴、Wittig-Horner缩合、还原等反应得到(±)-2-(1,2,6,7-四氢-8H-茚并[5,4-b]呋喃-8-基)乙胺,以L-(-)-二苯甲酰酒石酸拆分后与丙酰氯缩合得到失眠症治疗药物雷美替胺,总收率约5%,各步产物均无需柱色谱分离纯化。
Ramelteon was synthesized from 2,3-dihydrobenzofuran by Vilsmeier-Haack reaction, Wittig-Homer condensation and reduction to give ethyl 3-（2,3-dihydro-l-benzofuran-5-yl）propinate, which was subjected to dibromo substitution with I2 as catalyst, hydrolysis, cyclization, debromination, Wittig-Horner condensation and reduction to afford （±） -2- （1,2,6,7-tetrahydro-8H-indeno [5,4-b] furan-8-yl） ethylamine, followed by resolution with L- （-） -DBTA and condensation with propionyl chloride in 5 % overall yield.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2009年第3期161-164,共4页
Chinese Journal of Pharmaceuticals
关键词
雷美替胺
失眠症
拆分
合成
ramelteon
insomnia
resolution
synthesis
