Coupling between 2,7-dichloroxanthene-9-carboxylic acid (I) and 4-amino-1-tert-butoxycarbonylpiperidine (II) in the presence of EDC and HOBt afforded amide (III). After acidic cleavage of the Boc protecting group of (III), the resulting amine (IV) was reductively condensed with 1-cyclooctene carbaldehyde (V) by means of NaBH(OAc)3 to yield the cyclooctenylmethyl amine (VI). Subsequent alkylation of the tertiary amine (VI) with iodoethane gave rise to the target ammonium salt. Separation of the geometric isomers was carried out by column chromatography.
Cyclooctanone tosylhydrazone was treated with n-BuLi and subsequently reacted with DMF to afford (II). Compound (III) was prepared from 4-tert-butoxycarbonylpiperidine by reductive alkylation with (II). Deprotection of (III) and condensation with 2,7-dichloroxanthen-9-carboxylic acid (IV) using 1,1'-carbonyldiimidazole (CDI) afforded (V). Compound (V) was quaternarized with iodoethane to provide a quaternary ammonium derivative as a mixture of two isomers (cis and trans) attributed to the 4-substituted piperidinium structure in a ratio of 2:1. Finally, the mixture was separated by silica gel column chromatography to give a major isomer, J-113863.