(R)-5-(1-羟基-2-溴乙基)水杨酰胺醋酸酯的合成  

Synthesis of(R)-5-(1-hydroxyl-2-bromoethyl) salamide acetate

作　　者：赵璇[1] 张丹[1] 尹璐[1] 赵祥敏[2] 贾娴[1] 

机构地区：[1]沈阳药科大学制药工程学院,辽宁沈阳110016 [2]沈阳药大药业有限责任公司,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2009年第5期366-368,408,共4页Journal of Shenyang Pharmaceutical University

基　　金：国家自然科学基金资助项目(20472116);辽宁省博士科研启动基金资助项目(1050155)

摘　　要：目的优化关键手性中间体(R)-5-(1-羟基-2-溴乙基)水杨酰胺醋酸酯的合成工艺。方法以水杨酸为原料,经过酯化、氨解、付克酰基化、α-溴代、乙酰化5步反应得到5-溴乙酰水杨酰胺醋酸酯,其在手性催化剂钌-单磺酰化1,2-二苯基乙二胺((S,S)-Ru-TsDPEN)的催化下发生不对称转移氢化,得到(R)-5-(1-羟基-2-溴乙基)水杨酰胺醋酸酯。结果手性催化剂(S,S)-Ru-TsDPEN对5-溴乙酰水杨酰胺醋酸酯有较好的催化活性及对映体选择性,目标化合物总收率为31.5%,对映体过量百分率为80.8%。结论本方法为进一步研究拉贝洛尔的合成奠定了实验基础。Objective To prepare （R）-5-（1-hydroxyl-2-bromoethyl） salamide acetate. Methods 5-Bromoacetyl salarrfide acetate （7）was synthesized by using salicylic acid as starting material via a five steps process including esterification, ammonolysis, Friedel-Crafts acylation, α-bromination and acetylation. Compound 7 was subjected to transfer hydrogenation with chiral catalyst（S,S）-Ru-N-monosulfonated-1,2-diphe- nylethanediamine（（S,S）-Ru-TsDPEN） to afford the target compound. Results The desired product is synthesized in the overall yield of 31.5%. The chiral catalyst（ S, S）-Ru-TsDPEN shows good catalytic activity and enantioselectivity in transfer hydrogenation of compound 7 with 80.8% enantiomeric excess. Conclusions （R）-5-（ 1 -hydroxyl-2-bromoethyl） salamide acetate, which is a key chiral intermediate of labetalol, was synthesized by using chiral catalyst（ S, S）-Ru-TsDPEN in transfer hydrogenation so as to lay a foundation for further study on synthesis of labetalol.

关 键 词：拉贝洛尔 手性中间体 合成 

分 类 号：R914[医药卫生—药物化学]