N-tert-Butoxycarbonyl-α-(2-fluorobenzyl)-l-proline

In the title compound, C17H22FNO4, the pyrrolidine ring adopts an envelope conformation with the disordered components of the methylene C atom, with site occupancies of 0.896 (7) and 0.104 (7), being the flap on either side of the mean plane involving the other atoms of the ring. The carboxylic acid group forms dihedral angles of 72.06 (11) and 45.44 (5)° with the N-tert-butoxycarbonyl group and the 2-fluorobenzyl group, respectively. In the crystal, two-dimensional layers of molecules parallel to (001) are built through an R 4 4(23) motif generated via O—H⋯O, C—H⋯O and C—H⋯F interactions, and an R 2 2(11) motif generated by C—H⋯O and C—H⋯F interactions.

In the title compound, C 17 H 22 FNO 4 , the pyrrolidine ring adopts an envelope conformation with the disordered components of the methylene C atom, with site occupancies of 0.896 (7) and 0.104 (7), being the flap on either side of the mean plane involving the other atoms of the ring. The carboxylic acid group forms dihedral angles of 72.06 (11) and 45.44 (5) with the N-tert-butoxycarbonyl group and the 2fluorobenzyl group, respectively. In the crystal, two-dimensional layers of molecules parallel to (001) are built through an R 4 4 (23) motif generated via O-HÁ Á ÁO, C-HÁ Á ÁO and C-HÁ Á ÁF interactions, and an R 2 2 (11) motif generated by C-HÁ Á ÁO and C-HÁ Á ÁF interactions.

Rosli Comment
Modified amino acids are known to enhance the chemical, physical and biological properties of proteins (Anderson et al., 2004). Also, due to their structural diversity and functional versatility, they are widely used as chiral building blocks and molecular scaffolds in pharmaceutics (Taylor et al., 1998;Ryder et al., 2000;Jeng et al., 2002). N-Butoxycarbonyl-(S)-αbenzyl proline, a closely related analogue of the title compound N-tert-butoxycarbonyl-α-(2-fluorobenzyl)-L-proline, is a potential non-nucleoside reverse transcriptase inhibitor in anti-human-immunodeficiency virus type-1 (Tamazyan et al.,
The acetonitrile was removed in vacuo and residue was partitioned between ether (20 ml) and water (10 ml). The aqueous layer was washed with ether (10 ml) and acidified with 10% aqueous citric acid to pH 3-4. The aqueous layer was extracted with ethyl acetate (3 × 10 ml) and combined organic extracts were washed with brine solution (1 × 10 ml), dried over Na 2 SO 4 , and concentrated to yield N-tert-butoxycarbonyl-α-(2-fluorobenzyl)-L-proline (m.p. 430-433 K) as a white solid. Crystals were grown from ethanolic solution by slow evaporation at room temperature.

Refinement
All H atoms, except hydroxy H1 atom, were placed at geometrically calculated positions (0.99 Å for methylene C-H, 0.98 Å for methyl C-H and 0.95 Å for aromatic C-H) and refined using a riding model. The U iso values of all H atoms were constrained to 1.2U eq (1.5 times for hydroxyl and methyl H atoms) of the respective atom to which the H atom bonds. The hydroxy H1 atom was freely refined. In the pyrrolidine ring, the C4 atom exhibits disorder (resolved into C4A and C4B) and the same was modelled using SIMU and SADI restraints leading to site-occupancies of 0.896 (7) and 0.104 (7). In the absence of significant anomalous scattering effects 1492 Friedel pairs were merged. The enantiomer has been assigned by reference to an unchanging chiral centre in the synthetic procedure.   Part of the crystal structure of the title compound, showing R 2 2 (11) and R 4 4 (23) motifs through a combination of O-H···O, C-H···O and C-H···F hydrogen bonds and the formation of a two dimensional layer parallel to the ab plane. For the sake of clarity, H atoms not involved in hydrogen bonding have been omitted.

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 R-factors(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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq Occ. (