酒石酸阿福特罗的合成工艺研究  

Study on Synthesis Process of Arformoterol Tartrate

作　　者：陈娇 曹明玉 秦贞苗[1] 张小坡[1] CHEN Jiao;CAO Ming-yu;QIN Zhen-miao;ZHANG Xiao-po(School of Pharmacy,Hainan Medical University,Hainan Haikou 571199,China)

机构地区：[1]海南医学院药学院,海南海口571199

出　　处：《广州化工》2023年第3期117-119,共3页GuangZhou Chemical Industry

摘　　要：以3′-硝基-4′-苄氧基-2-溴苯乙酮(2)为起始原料,经手性不对称还原、硝基还原和甲酰化、分子内环合和缩合、脱苄基保护基和精制制得酒石酸阿福特罗。不对称还原体系为硼烷二甲硫醚/(1 R,2 S)-1-氨基-2-茚醇,纯化溶剂为甲苯和异丙醚。硝基的还原体系为10%Pt/C/Me_(2)S,酰化剂为甲酸-乙酸酐混酐。4的分子内环合温度为30~35℃,缩合温度为110~120℃,脱保护压力为1.2~1.5 MPa,纯化溶剂为乙醇/纯化水。改进的制备方法克服了文献所报道的制备工艺的一些缺点。Arformoterol Tartrate was synthesized from 1-(4-(Benzyloxy)-3-nitrophenyl)-2-bromoethanone as the start material via chiral asymmetry reduction,nitro-group reduction and formylation,intramolecular cyclization and condensation,debenzyl protective group and purification.The reducing agent of borane dimethyl sulfide complex anf(1 R,2 S)-1-amino-2,3-dihydro-1 H-inden-2-ol was used in the synthesis of intermediate 3,and the purified solvent was toluene and isopropyl ether.The reducing agent of the nitro group was 10%Pt/C and dimethyl sulfide,the acylating agent was formic acid-acetic anhydride mixed anhydride.The intramolecule-ar cyclic binding temperature of 4 was 30 to 35℃,the condensation temperature was 110 to 120℃,and the deprotection pressure was 1.2 to 1.5 MPa,the purified solvent was ethanol/purified water.Some drawbacks in the literatures were improved.

关 键 词：酒石酸阿福特罗 合成 工艺优化 

分 类 号：R914[医药卫生—药物化学]