(S)-tert-Butyl 3-(3-phenyl-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate

The title compound, C18H23N3O3, crystallized with two independent molecules (A and B) in the asymmetric unit. The phenyl ring and the 1,2,4-oxadiazole ring are inclined to one another by 19.9 (3)° in molecule A and 7.3 (3)° in molecule B. The absolute structure of the title compound was referred to the transfered chiral center (S) of one of the starting reactants. In the crystal, A molecules are linked by C—H⋯N interactions involving the two oxadiazole N atoms.

The title compound, C 18 H 23 N 3 O 3 , crystallized with two independent molecules (A and B) in the asymmetric unit. The phenyl ring and the 1,2,4-oxadiazole ring are inclined to one another by 19.9 (3) in molecule A and 7.3 (3) in molecule B. The absolute structure of the title compound was referred to the transfered chiral center (S) of one of the starting reactants. In the crystal, A molecules are linked by C-HÁ Á ÁN interactions involving the two oxadiazole N atoms.
followed by deprotection of the protective group, to give many usefull compounds.
The title compound crystallized in the chiral monoclinic space group P2 1 , with two independent molecules (A and B) in the asymmetric unit (Fig. 1). It was obtained from a chiral source, hence its absolute structure, (S), was confirmed by the transfered chiral center; atom C9 in molecule A and atom C27 in molecule B (Fig. 1). The bond distances in the two molecules are very similar and close to normal values (Allen et al., 1987). The two molecules differ in the orientation of the phenyl ring with respect to the oxadiazole mean plane. In molecule A this dihedral angle is 19.9 (3)°, while in molecule B it is only 7.3 (3)°. In both molecules the piperidine ring has a chair conformation.
In the crystal symmetry related A molecules are linked via C-H···N interactions (see Table 1 and Fig. 2 for details).

Experimental
A suspension of hydroxylamine hydrochloride (4.09 g), potassium carbonate (2.76 g), benzonitrile (1.03 g) in absolute ethanol (200 mL) was heated at reflux for 10 h. After the reaction was completed, monitored by TLC, the mixture was cooled, filtered to remove inorganic salts, and concentrated under vacuum. The residue was purified by column chromatography, by use of a gradient elution of dichloromethane to 40% acetone in dichloromethane, to give (E)-N-hydroxybenzamidine (1.36g). 1 H NMR (300 MHz, DMSO-d6): 9.59 (s, 1H), 7.62-7.67 (m, 2H), 7.32-7.37 (m, 3H), 5.77 (s, 2H); EI (M+) 136 A mixture of (S)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (1.15 g) in absolute THF (50 mL), isobutyl carbonochloridate (5ml) and trimethylamine (2ml) were mixted together and stirred for 30min at rt, followed by slow dropwise addition of (E)-N-Hydroxy-benzamidine (1.36g) in THF (15mL). After the reaction was completed, monitored by TLC, the mixture was injected into n-Bu4NF (1 M in THF, 3 mL), warmed to reflux and was stirred for 24 h. After this reaction was completed, monitored by TLC, the mixture was poured into EtOAc and washed with water and brine. The organic layer was dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography by use of a gradient elution of EtOAc/hexanes. The material was crystallized from EtOH to give the title compound as a white solid. Colourless-rod-like crystals, suitable for X-ray analysis, were obtained by recrystallization from EtOH. 1

Refinement
In the final cycles of refinement, in the absence of significant anomalous scattering effects, 4120 Friedel pairs were merged and Δf " set to zero. The H-atoms could all be located in difference Fourier maps. In the final cycles of refinment they were placed in calculated positions and treated as riding atoms: C-H 0.93, 0.96, 0.97 and 0.98 Å, for H-methine, H-methyl, H-methylene and H-aromtic, respectively, with U iso (H) = k × U eq (C), where k = 1.5 for H-methyl and = 1.2 for all other H-atoms. Fig. 1. The molecular structure of the two independent molecules (A and B) of the title compound, with atom labels and 30% probability displacement ellipsoids.  Table 1 for details).