合成路线1

A) Synthesis of intermediate (VII): The hexanophenone (I), prepared by Freidel-Crafts acylation of anisole with hexanoyl chloride, was condensed with lithioacetonitrile to generate the carbinol (II), which was then dehydrated using trifluoroacetic acid in dichloromethane to produce the unsaturated nitrile (III) predominantly as its (E)-isomer (E/Z ratio > 12:1). Reduction of the newly formed alpha,beta-unsaturated nitrile with diisobutylaluminum hydride furnished the (E)-octenal (IV), which was then treated with the stabilized ylid (carbomethoxymethylene)triphenylphosphorane to yield the dienoic acid ester (V). While use of a polar reaction medium such as methanol or ethanol in this Wittig reaction resulted in mixtures of isomers with an E/Z ratio as high as 3:2 around the newly introduced double bond, formation of the (Z)-isomer could be minimized (< 7%) through the use of an aprotic reaction solvent, e.g., dichloromethane or benzene. In preparation for its conversion to the target carboxamide, the (E,E)-decadienoic acid ester was saponified and the resulting acid (VI) condensed with p-nitrophenol in the presence of dicyclohexylcarbodiimide to yield the highly reactive p-nitrophenyl ester (VII).