Treatment of 2,2-dimethylcyclopentanone (I) with tosylmethyl isocyanide and potassium tert-butoxide produced nitrile (II), which was reduced to amine (III) employing LiAlH4 in THF. Coupling of amine (III) with mono-methyl terephthalate (IV) by means of EDC and HOBt gave amide (V). The target oxadiazole system was then obtained by condensation of (V) with N-hydroxypentamidine (VI) in the presence of NaH, and the (S)-enantiomer was isolated by using chiral HPLC.

Amine (III) was synthesized from 2,2-dimethylcyclopentanone (I) by treatment with tosylmethyl isocyanide, followed by reduction of the resultant nitrile (II) with LiAlH4. Condensation of 4-cyanobenzoic acid (IV) with amine (III) produced the corresponding amide (V). Subsequent addition of hydroxylamine to the cyano group of (V) gave rise to the hydroxyamidine (VI). The target oxadiazole derivative was then obtained by condensation of (VI) with 4,4,4-trifluorobutyric acid (VII), followed by cyclization under basic conditions. Separation of the enantiomers was carried out by chiral preparative HPLC.