醋酸氟卡尼的合成工艺优化

A novel synthetic process of flecainide acetate

摘要:

以廉价的商业化试剂5-溴-2-碘苯甲酸为原料，经Ullmann醚化、酸胺缩合、成盐等反应制备出醋酸氟卡尼，反应总收率达54.2%(以5-溴-2-碘苯甲酸计)。并对关键的Ullmann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}为配体时 ，以DMF为溶剂，110℃反应12h。中间体收率达60.1%。改进工艺路线后醋酸氟卡尼总收率为54.0%，纯度为99.93%。中间体及产物经1H NMR、MS等确证。

Abstract:

flecainide acetate was synthesized from methyl 5-bromo-2-iodobenzoic acid via Ullmann aryl etherification, amide condensation, salification. The total yield was 52.1% (based on methyl 5-bromo-2-iodobenzoic acid). The optimistic condition of Ullmann aryl etherification reaction was established. The reaction conditions were obtained as follows: when{[(phen)2Cu][OCH2CF3]Cu} is used as ligand. The reaction was stirred in DMF at 110℃for 12 hours. The yield of key intermediate is 60.1%. The total yield of flecainide acetateis 54.0%, and the purity is 99.93%. The structure of flecainide acetate and the important intermediates were confirmed by MS, 1H NMR.