Addition of cyclopropylmagnesium bromide (II) to dibenzocycloheptanone (I) afforded the carbinol adduct (III), which was further rearranged to the bromopropylidene derivative (IV) upon treatment with bromotrimethylsilane. Alkylation of ethyl (R)-nipecotate (V) with bromide (IV) gave the tertiary amine (VI). The ethyl ester group of (VI) was finally hydrolyzed under basic conditions to furnish the corresponding carboxylic acid.
The condensation of dibenzocycloheptylidene derivative (I) with radiolabelled piperidine-3-carboxylic acid ethyl ester (II) by means of K2CO3 in ethyl acetate gives the adduct (III), which is hydrolyzed with aqueous HCl to yield the carboxylic acid (IV). Finally, this compound is submitted to optical resolution by means of chiral chromatography to provide the chiral radiolabelled compound.
The reduction of 1-[3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propyl]-1,2,5,6-tetrahydropyridine-3-carboxylic acid (I) with tritium over PdO in methanol gives the racemic ditritiated compound (II), which is then submitted to optical resolution by chiral chromatography to afford the chiral radiolabelled compound.