3-(2,5-Dimethylphenyl)-8-methoxy-2-oxo-1-azaspiro[4.5]dec-3-en-4-yl 3-(2-bromo-4-fluorophenyl)acrylate

In the title compound, C27H27BrFNO4, which is an inhibitor of acetyl-CoA carboxylase, the cyclohexane ring displays a chair comformation with the spiro-C and methoxy-bearing C atoms deviating by 0.681 (7) and −0.655 (1) Å, resppectively, from the mean plane formed by the other four C atoms of the spiro-C6 ring. The mean planes of the cyclohexane and 2-bromo-4-fluorophenyl rings are nearly perpendicular to that of the pyrrolidine ring, making dihedral angles 89.75 (6) and 87.60 (9)°, respectively. In the crystal, molecules are linked via pairs of N—H⋯O hydrogen bonds, forming inversion dimers.

In the title compound, C 27 H 27 BrFNO 4 , which is an inhibitor of acetyl-CoA carboxylase, the cyclohexane ring displays a chair comformation with the spiro-C and methoxy-bearing C atoms deviating by 0.681 (7) and À0.655 (1) Å , resppectively, from the mean plane formed by the other four C atoms of the spiro-C 6 ring. The mean planes of the cyclohexane and 2-bromo-4fluorophenyl rings are nearly perpendicular to that of the pyrrolidine ring, making dihedral angles 89.75 (6) and 87.60 (9) , respectively. In the crystal, molecules are linked via pairs of N-HÁ Á ÁO hydrogen bonds, forming inversion dimers.
Encouraged by previous papers from our laboratory (Zhao et al., 2012;Wang et al., 2011) in order to find the relationship between the ester at position C3 and biological activity, we synthesized the title compound by an esterification reaction and determined its molecular and crystal structure (Fig. 1).
The molecule contains two benzene rings, one six membered ring, and one five membered ring. The cyclohexane ring displays a chair conformation; atoms C22, C23, C25 and C26 lie in a plane with atoms C4 and C24 deviating by 0.681 (7) and -0.655 (1) Å. The mean plane of the cyclohexane ring and the benzene ring C16-C21 are nearly perpendicular to the pyrrolidine ring, making dihedral angles of 89.75 (6) and 87.60 (9) °, respectively. In the crystal, molecules are linked via a pair of N-H···O hydrogen bonds forming inversion dimers (Table 1).

Experimental
The synthesis of the title compound is described in Fig. 2. In a flask, a solution of 3-(2-bromo-4-fluoro-phenyl)-acryloyl chloride (0.55 g, 2.0 mmoL) in anhydrous chloroform (5 ml) was added drop wise to a solution of cis-3-(2,5-dimethylphenyl)-4-hydroxy-8-methoxy-1-azaspiro[4.5]dec-3-en-2-one (0.40 g, 1.3 mmoL) in anhydrous chloroform (15 ml) at 0° C and stirred for 10 min. The reaction mixture was allowed to warm to room temperature and stirred at room temperature for 1 h. The reaction mixture was then washed with water (15 ml), saturated sodium bicarbonate (15 ml) and saturated sodium chloride solution and dried over anhydrous Na 2 SO 4 . The solvent was evaporated, and the residual solid was purified by flash column chromatography on silica gel using a mixture of petroleum ether (boiling point range 60-90° C) and ethyl acetate (4:1 by volume) as the eluent to give the title compound (0.33 g, 48%) as a colorless solid. The solid was filtrated and recrystallized with 95% ethanol to get colourless blocks.

Figure 1
The molecular structure of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 40% probability level.  Reaction scheme.

Special details
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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.