Flecainide acetate, E-0735, R-818, Apocard, Tambocor

醋酸氟卡胺 氟卡尼 Chemical Name: N-(2-Piperidylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide monoacetate
CAS No. 54143-56-5, 54143-55-4 (free base)
项目整合开发状态: Launched-1982
项目研究机构: 3M Pharmaceuticals (Originator), Eisai (Licensee)
合成路线:The etherification of hydroquinone (I) with 2,2,2-trifluoroethyl trifluoromethanesulfonate (II) by means of K2CO3 in refluxing acetone gives the corresponding diether (III),which is submitted to a Friedel-Crafts condensation with Ac-Cl or Ac2O and AlCl3 in dichloromethane yielding the acetophenone (IV).The chlorination of (IV) with Cl2 in acetic acid at 55 C gives the alpha,alpha-dichloroacetophenone (V),which is further chlorinated with Cl2 and NaOAc in acetic acid at 100 C affording the corresponding trichloro derivative (VI).The reaction of (VI) with 2-(aminomethyl)pyridine (VII) in cyclohexane/toluene or isopropanol furnishes the benzamide (VIII),which is finally hydrogenated with H2 over Pt/C in isopropanol/acetic acid to give the target piperidine derivative.