Synthesis of the water-soluble adenosine A1 receptor antagonist FR166124 through a novel sequential Horner-Emmons/isomerization reaction

Article abstract of DOI:10.1016/S0040-4020(99)00590-6

An efficient synthesis of FR166124 (1) was achieved through a novel sequential Horner-Emmons - isomerization reaction of cyclohexanone (2) with tert-butyl diethylphosphonoacetate (3) as the key process. Extensive studies of the key reaction indicated that temperature, base and conformation of the Horner-Emmons products were important factors in the isomerization reaction, leading to a proposed mechanism for this unusual Horner-Emmons reaction.