N-Benzyl-N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propanamine (N-benzylflouoxetine)

In the title compound, C24H24F3NO, the N-benzyl derivative of fluoxetine {N-methyl-3-[4-(trifluoromethyl)phenoxy]benzenepropanamine}, the three aromatic rings A, B and C are inclined to one another by 76.77 (12)° for A/B, 17.05 (14)° for A/C and 89.66 (14)° for B/C. In the crystal structure, molecules are linked via C—H⋯π interactions to form one-dimensional chains propagating in the [010] direction.

In the title compound, C 24 H 24 F 3 NO, the N-benzyl derivative of fluoxetine {N-methyl-3-[4-(trifluoromethyl)phenoxy]-benzenepropanamine}, the three aromatic rings A, B and C are inclined to one another by 76.77 (12) for A/B, 17.05 (14) for A/C and 89. 66 (14) for B/C. In the crystal structure, molecules are linked via C-HÁ Á Á interactions to form onedimensional chains propagating in the [010] direction.

Comment
Fluoxetine (N-methyl-3-[4-(trifluoromethyl)phenoxy]benzenepropanamine) has been approved worldwide in the therapy of major depression (Markowitz et al., 1999);Feighner & Boyer, 1991) and in the treatment of other syndromes, such as Bulimia nervosa, Panic fits and obsessive-compulsive disorder (Benefield et al., 1986;Wong et al., 1995). Recently, Zhu et al. reported that continuous Fluoxetine administration also prevents recurrence of pulmonary arterial hypertension in rats (Zhu et al., 2009). Crystal structure of Fluoxetine has been reported as the hydrochloride, hydrochloride benzoic acid, hydrochloride succinic acid and hydrochloride fumaric acid (Robertson et al., 1988;Childs et al., 2004). Herein, we report on the crystal structure of N-Benzyl Fluoxetine.
The molecular structure of the title molecule is illustrated in Fig. 1. The geometrical parameters are similar to those in the above mentioned derivatives. In the title compound the F atoms of the CF 3 groups shows disorder and were modelled with three different orientations (F1a-F3a, F1b-F2b and F2aa-F2ab-F3bb-F3ba) with occupancy factors of 0.50, 0.50 and 0.25, respectively (Fig. 1). The H7-C7-C8-C9 torsion angle is -19.2°, indicating that the monosubstituted phenyl ring (B) deviates only slightly from the plane defined by atoms C8, C7, and H7.
In the crystal structure of the title compound, there are no intra-or intermolecular hydrogen-bonding interactions, only weak C-H···π interactions. These lead to the formation of a chain propagating along [010]; see Fig. 2 and Table 1.

Experimental
A mixture of Fluoxetine hydrogen chloride 0.5 g (1.45 mmol), sodium hydride 0.14 g (5.8 mmol) and N,N-dimethylformamide (10 ml) was stirred at room temperature for 30 min, followed by the addition of benzyl chloride 0.33 ml (2.9 mmol).
Stirring was continued for a period of 3 h and the contents were then poured over crushed ice. The precipitated product was isolated, washed and crystallized from methanol, giving colourless prism-like crystals, suitable for X-ray analysis.

Refinement
The F atoms of the CF 3 group shows disorder and they were modelled with three different orientations (F1a/F3a, F1b/F2b and F2aa/F2ab/F3bb/F3ba) with occupancy factors of 0.50, 0.50 and 0.25, respectively The C-bound H atoms were included in calculated positions and refined using a riding model: C-H = 0.98, 0.97, 0.96 and 0.93 Å, for methine, methylene, methyl and aromatic H atoms, respectively, with U iso (H) = k × U eq (C), where k = 1.2 for methine, methylene and aromatic H atoms and = 1.5 for methyl H atoms. Fig. 1. A view of the three independent molecules of the title compound, showing the atomnumbering scheme and 30% probability displacement ellipsoids.

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.
Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating Rfactors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.