醋酸氟卡尼的合成工艺优化  

Synthesis process optimization of flecainide acetate

作　　者：曹宁 卢丹 张建斌 庄子翀 卢建媚 CAO Ning;LU Dan;ZHANG Jianbin;ZHUANG Zichong;LU Jianmei(Guangzhou Baihua Flavours and Fragrgances Co.,Ltd.,Guangzhou 510663,Guangdong,China)

机构地区：[1]广州百花香料股份有限公司,广东广州510663

出　　处：《精细化工》2023年第5期1107-1112,共6页Fine Chemicals

摘　　要：以5-溴-2-碘苯甲酸为原料,经Ullmann芳基醚化、酸胺缩合、成盐反应步骤制备出醋酸氟卡尼。并对Ullmann芳基醚化反应条件进行优化。结果表明,当以[双-(1,10-菲啰啉铜)](三氟乙氧基)铜为配体、N,N-二甲基甲酰胺(DMF)为溶剂、110℃反应12h,中间体2,5-二(2,2,2-三氟乙氧基)苯甲酸收率达60.1%。改进工艺路线后醋酸氟卡尼总收率为54.2%(以5-溴-2-碘苯甲酸计),HPLC纯度为99.93%。中间体及产物结构经NMR、MS确证。Flecainide acetate was synthesized from 5-bromo-2-iodobenzoic acid via Ullmann aryl etherification,amide condensation and salification process with an overall yield of 54.2%(based on 5-bromo-2-iodobenzoic acid).The conditions of Ullmann aryl etherification reaction were optimized.The results showed that,when the reaction was conducted at 110℃for 12 h with[bis-(1,10-phenanthrolinecopper)](trifluoroethoxy)copper used as ligand and N,N-dimethylformamide(DMF)as solvent,the yield of intermediate 2,5-bis(2,2-trifluoroethoxy)benzoic acid reached up to 60.1%.The total yield of flecainide acetate was 54.0%,and HPLC purity was 99.93%.The structure of intermediates and products were confirmed by NMR and MS.

关 键 词：醋酸氟卡尼 Ullmann芳基醚化 酸胺缩合 工艺优化 医药原料 

分 类 号：TQ463[化学工程—制药化工]