4-(3,3-Dimethylperhydro-1,3-oxazolo[3,4-a]pyridin-1-yl)-2,8-bis(trifluoromethyl)quinoline

An L-shaped conformation is found in the title molecule, C20H20F6N2O, the C—C—C—C torsion angle linking the two fused-ring systems being −92.80 (19)°. The oxazole ring adopts an envelope conformation [the N atom lies 0.579 (2) Å out of the plane defined by the remaining atoms], and the piperidine ring has a chair conformation. Supramolecular chains are found in the crystal structure that are sustained by C—H⋯π and π–π [3.6089 (10) Å] interactions.

An L-shaped conformation is found in the title molecule, C 20 H 20 F 6 N 2 O, the C-C-C-C torsion angle linking the two fused-ring systems being À92. 80 (19) . The oxazole ring adopts an envelope conformation [the N atom lies 0.579 (2) Å out of the plane defined by the remaining atoms], and the piperidine ring has a chair conformation. Supramolecular chains are found in the crystal structure that are sustained by C-HÁ Á Á and -[3.6089 (10) Å ] interactions.
The use of the EPSRC X-ray crystallographic service at the University of Southampton, England and the valuable assistance of the staff there is gratefully acknowledged. JLW acknowledges support from CAPES and FAPEMIG (Brazil).

Comment
Mefloquine, manufactured as the racemic erythro hydrochloride salt is a synthetic analogue of quinine used in the prevention and treatment for malaria in combination with other drugs (Maguire et al., 2006). However, despite its efficacy, this orally-administered drug possesses several important physical and psychological adverse side-effects, such as birth defects, anxiety, aggression, seizures, nightmares, neuropathy, insomnia, central nervous system problems, acute depression, urinary disorders, etc. (Croft & Herxheimer, 2002). Due to these effects, mefloquine analogues have been synthesized with the goals of increasing the efficacy and eliminating adverse side-effects (Lima et al., 2002;Biot et al., 2000;Roesner et al., 1981).
Oxazolidines are frequently prepared from 2-amino-1-hydroxyalkanes and carbonyl compounds (Bergmann et al., 1953;Oh et al., 2000;Saba et al., 2007;Page et al., 2007); in particular cases, azeotropic removal of water or the use of a catalyst is involved (Page et al., 2007). However, problems of stability of oxazolidines and formation of tautomeric mixtures of the oxazolidines and the corresponding imines can limit or complicate this synthetic route (Page et al., 2007).
1,3-Oxazolidine derivatives, in general, have been shown to have useful biological activities (Moloney et al., 1998;Andes et al., 2002;Kumar et al., 2009). The title compound, (I), was isolated unexpectedly from a solution of mefloquine hydrochloride and 2-hydroxybenzoic acid in acetone, followed by initial by recrystallisation from isopropanol, and finally from EtOH.

Experimental
A mixture of racemic erythro mefloquinium chloride (1 mmol) and 2-hydroxybenzoic acid (1 mmol) in acetone (20 ml) was refluxed for 3 h. The reaction mixture was rotary evaporated and the residue was taken up in isopropanol. Two crops of crystals were collected on maintaining the solution at room temperature. From the second crop, on recrystallisation from EtOH, a small amount of the title compound was obtained, m.p. 424-426 K.