(S)-2-[(4-Fluorophenyl)formamido]-3-phenylpropanoic acid

The crystal structure exhibits monoclinic (P21) symmetry at room temperature. The two molecules in the asymmetric unit of the title compound, C16H14FNO3, exhibit different torsion angles along the central sp 3 C—N bonds and are linked together through two N—H⋯O hydrogen-bonding interactions.

The title compound, C 16 H 14 FNO 3 , was synthesized via solid phase methods; it exhibits monoclinic (P2 1 ) symmetry at room temperature. The two independent molecules that comprise the asymmetric unit display distinct torsion angles of 173.2 (2) and 72.6 (2) along the central sp 3 C-N bond. In the crystal, hydrogen bonding through N-HÁ Á ÁO contacts couples the asymmetric unit molecules into pairs that align in layers extending parallel to (100) via additional O-HÁ Á ÁO interactions. The phenyl ring of one independent molecule was found to be disordered over two sets of sites in a 0.55 (3):0.45 (3) ratio.

Structure description
Antibiotic resistance is a major global concern, compounded by the shortage of novel classes of antibiotics in the clinical pipeline (Friedman et al., 2016;Frieri et al., 2017). In order to address the need for new pharmaceuticals and to incorporate drug discovery into the undergraduate curriculum, William Scott and coworkers created the Distributed Drug Discovery (D3) program ). D3 0 s virtual catalogs enumerate sets of amino-acid derivatives that have potential biological activity and that may be synthesized through straightforward combinatorial methods Abraham et al., 2017). The D3 Lab 2 procedure targets N-acyl derivatives of natural amino acids in three steps (Dounay et al., 2019). In this paper, we report the use of the D3 procedure to obtain the title compound as a single stereoisomer.
The compound was synthesized via solid phase methods starting from an Fmocprotected phenylalanine bound to a Wang resin, which was purchased from CreoSalus Advanced Chem Tech as the enantiopure S stereoisomer. The stereocenter remains unchanged during the deprotection, benzoylation, cleavage sequence to form the final data reports product. The absolute configuration of the title compound has been established by anomalous dispersion effects in the diffraction measurement.
Two unique molecules comprise the asymmetric unit. Within the molecules the planes containing the benzene rings are rotated with respect to one another by 79.9 (1) (molecule 1, containing N1-F1) and 89.3 (1) (molecule 2, containing N2-F2), as shown in Fig. 1. The phenyl ring in molecule 1 is disordered over two slightly different positions. Interestingly, torsion angles measured at the middle of the molecules are quite different; in molecule 1, the C1-N1-C9-C10 angle is 173.2 (2) and in molecule 2, the analogous C17-N2-C25-C26 angle is 72.6 (2) . The amino-hydrogen atom on each molecule is hydrogen-bonded to the organic-acid carbonyl O atom on the other molecule (N-HÁ Á ÁO contacts, Table 1) coupling the molecules in the asymmetric unit so that they are positioned on top of each other with a fluoro-substituted ring above and nearly perpendicular to the unsubstituted ring of the partner molecule [mean dihedral angle between the rings of the two molecules = 87 (3) ]. Fig. 2 shows an overlay of the two distinct molecules, highlighting their conformational differences. As shown in Fig. 3, the coupled asymmetric-unit pairs align in chains parallel to [010] via additional hydrogenbonding interactions between OH organic-acid hydrogen atoms and the amide oxygen atoms in adjacent pairs through the O-HÁ Á ÁO contacts listed in Table 1. Layers of chains extending parallel to (100) are visible when the packing is viewed along the b axis. The benzene-ring ends of the asymmetric-unit pairs that project out of each hydrogen-bonded chain occupy the voids between coupled asymmetric-unit pairs in the chain layers above and below, allowing closer packing.

Synthesis and crystallization
50 mmol of S-phenylalanine protected with fluorenylmethyloxycarbonyl (Fmoc) and bound to a Wang resin were placed in a fritted vial with screw caps at both ends. The resin was rinsed with three 3 ml aliquots of N-methyl-2-pyrrolidone (NMP) and three 2 ml aliquots of NMP:piperidine (4:1). The bottom of the vial was capped to prevent the acylating reagents from draining from the vial. To the resin was added 1.0 ml of a solution of p-fluorobenzoic acid (0.25 M) and hydroxybenzotriazole (HOBt, 0.25 M) in NMP and 0.5 ml of 0.5 M diisopropylcarbodiimide in NMP. The vial was capped, inverted three times, and allowed to sit. After four days, the vial was uncapped at both ends, and the resin was washed The asymmetric unit consists of two molecules of the title compound, shown here with displacement ellipsoids drawn at the 50% probability level. The minor component of the disordered phenyl ring is shown in pale blue. Table 1 Hydrogen-bond geometry (Å , ). Symmetry codes: (i) Àx þ 1; y þ 1 2 ; Àz þ 2; (ii) Àx þ 1; y À 1 2 ; Àz þ 1.

Figure 2
An overlay illustration of the two independent molecules. For molecule 1 only the major component of the disordered phenyl ring is displayed; molecule 2 is shown in purple.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The phenyl ring (C11-C16) of molecule 1 was found to be disordered over two sets of sites in a ratio of 0.55 (3):0.45 (3). The AFIX 66 constraint was applied to both parts of the disordered phenyl ring, and the RIGU rigid body restraint was applied to all non-hydrogen atoms in those rings with values of 0.001 for the 1-2 and 1-3 distances.   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.