新产品编号:1916311

Chemical Name: 7endo-Fluoro-3endo-(4-fluorophenyl)-8-methyl-2exo-propyl-8-azabicyclo[3.2.1]octane
项目整合开发状态: Preclinical
项目研究机构: Georgetown University (Originator), Northeastern University (Originator), UT Medical Branch at Galveston (Originator)
合成路线:The dipolar cycloaddition of betaine (I) with (R)-p-tolyl vinyl sulfoxide (II) produced a mixture of exo and endo cycloadducts (III).Flash chromatography of the reaction mixture led to the separation of the exo tropenones as a diastereomeric mixture,and further crystallization from EtOAc provided the pure major isomer (IV).Copper-catalyzed conjugate addition of n-propylmagnesium bromide to the unsaturated ketone (IV) gave (V).The keto group was then reduced to alcohol (VI) using LiBH4.Tropane (VIII) was obtained by Barton deoxygenation of tropanol (VI) via conversion to thiono carbonate (VII) and subsequent reduction with Bu3SnH.Oxidation of the sulfoxide group to sulfone (IX) was carried out by means of oxone in aqueous MeOH.Fluorination with N-fluorobenzenesulfonimide gave the beta-fluoro compound (X).Finally,reductive desulfonation with sodium amalgam yielded the title compound.