Benzyl 2-{[2,8-bis(trifluoromethyl)quinolin-4-yl](hydroxy)methyl}piperidine-1-carboxylate

The title molecule, C25H22F6N2O3, adopts an open conformation whereby the quinoline and carboxylate ester groups are orientated in opposite directions but to the same side of the piperidine ring so that the molecule has an approximate U-shape. The piperidine ring adopts a distorted boat conformation. In the crystal, inversion dimers linked by pairs of O—H⋯O hydrogen bonds generate R 2 2(14) loops.

The title molecule, C 25 H 22 F 6 N 2 O 3 , adopts an open conformation whereby the quinoline and carboxylate ester groups are orientated in opposite directions but to the same side of the piperidine ring so that the molecule has an approximate Ushape. The piperidine ring adopts a distorted boat conformation. In the crystal, inversion dimers linked by pairs of O-HÁ Á ÁO hydrogen bonds generate R 2 2 (14) loops.
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
For some decades, in combination with other drugs, mefloquine has been used in the prevention and treatment of malaria (Maguire et al., 2006). The activity of mefloquine has been investigated against other diseases more recently, for example, as anti-viral and anti-tubercular agents (Mao et al., 2007). In continuation of on-going structural and biological studies on mefloquine derivatives (Gonçalves et al., 2010(Gonçalves et al., , 2011a(Gonçalves et al., , 2011bWardell, et al., 2010;Pitaluga et al., 2010), we now report the crystal and molecular structure of the title compound, (I).
In the molecule of (I), Fig. 1, the hydroxyl group lies to one side of the plane through the quinolinyl residue and the substituted piperidine ring to other with the carboxylate ester directed away from the rest of the molecule. The residues lie to the same side of the piperidine ring so that the molecule has a U-shape. The piperidine ring has a distorted boat conformation with ring puckering parameters: q 2 = 0.7644 (16) Å; q 3 = -0.0283 (16) Å; QT = 0.7649 (16) Å; and θ = 92.12 (12) ° (Cremer & Pople, 1975). Mefloquine used as a reagent was a racemate. The sum of the angles at the trisubstituted N2 is 356° indicating a very near planar geometry, and hence an achiral centre. The configurations of the C12 and C13 in the illustrated molecule, Fig. 1, are R, S and R, respectively. The crystal structure contains an equal amount of the opposite enantiomer.
The most prominent intermolecular interactions in the crystal structure are O-H···O hydrogen bonds that lead to the formation of centrosymmetric dimeric aggregates via 14-membered {···HOC 2 NCO} 2 synthons, Fig. 1 and Table 1.

Refinement
The C-bound H atoms were geometrically placed (C-H = 0.95-1.00 Å) and refined as riding with U iso (H) = 1.2U eq (C). Fig. 1. The molecular structure of (I) showing displacement ellipsoids at the 50% probability level.