3-[(3S)-3-Ethyl-1-methylazepan-3-yl]phenyl N-(4-fluorophenyl)carbamate

The asymmetric unit of the title compound, C22H27FN2O2, a (−)-S-meptazinol derivative, contains two molecules. The azepane ring adopts a similar twist chair form in both molecules, while the dihedral angles between the two benzene rings are 88.17 (14) and 89.93 (14)° in the two molecules. The absolute configuration of the molecule was determined from the synthetic starting material. The crystal structure is stabilized by classical intermolecular N—H⋯O hydrogen bonds.

The absolute configuration of the azepane ring atom is C14(S), since the title compound was synthesized from (-)-S-meptazinol by esterification of the phenol group, which does not interfere with the chiral center C14.

Experimental
(-)-Meptazinol (200 mg, 0.86 mmol) was dissolved in anhydrous ether (5 ml) and a piece of Na metal (approximately 10 mg) was added. The mixture was stirred at room temperature for 30 min. Then 4-fluorophenylisocyanate (230 mg, 1.72 mmol) was added. The reaction mixture was continuously stirred for 4 h at room temperature and monitored by TLC. The precipitate was filtered off and the filtrate was evaporated to give yellow oil. The 10 ml H 2 O was added and pH of the aqueous layer was adjusted to 3 by 1N HCl, washed with Et 2 O, and then pH was adjusted to 10 by saturated Na 2 CO 3 aqueous solution. The resulting precipitate was filtered and washed with water three times. A white solid (yield 200 mg, 65.5%) was obtained. Single crystals suitable for X-ray analysis were obtained by slow evaporation of an acetonitrile solution.

Refinement
All H atoms were placed in the idealized positions with C-H = 0.93-0.96Å, and N-H = 0.86Å. The U iso (H) = 1.2-1.5 U eq (C,N).
The 3164 Friedel pairs were merged in crystal refinement procedure.

Special details
Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The 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.