Four stereoisomers of the novel μ-opioid receptor agonist tapentadol hydrochloride.

The crystal and mol­ecular structures of four stereoisomers of tapenta­dol hydro­chloride [systematic name: 3-(3-hy­droxy­phenyl)-N,N,2-trimethyl­pentan-1-aminium chloride], C14H24NO+·Cl−, a novel analgesic agent, have been determined by X-ray crystal structure analysis. Resolution of the isomers was carried out by reverse-phase and chiral high-performance liquid chromatographic (HPLC) methods. Stereoisomers (I) and (II) crystallize in the monoclinic space group P21, each with two tapenta­dol cations and two chloride anions in the asymmetric unit, while stereoisomers (III) and (IV) crystallize in the ortho­rhom­bic space group P212121, with one tapenta­dol cation and one chloride anion in the asymmetric unit. The absolute configurations of the four enantio­mers were determined unambiguously by X-ray crystallography. The crystal structures reveal the stereochemistries at the 3-ethyl and 2-methyl groups to be R,R, S,S, S,R and R,S in stereoisomers (I)–(IV), respectively. The ethyl and amino­propyl groups adopt different orientations with respect to the phenol ring for (I) and (IV). In all four structures, the chloride ions take part in N—H⋯Cl and O—H⋯Cl hydrogen bonds with the tapenta­dol mol­ecules, resulting in one-dimensional helical chains in the crystal packing in each case.