4-(3-Methoxyphenoxy)butyric acid

In the title compound, C11H14O4, an intermediate for the synthesis of a new kind of estrogen receptor modulator, all non-H atoms lie on a common plane (r.m.s. deviation = 0.0472 Å). All C—C bonds in the side chain are in a trans conformation, and the hydroxyl group is also trans to the methylene chain. In the crystal structure, molecules form centrosymmetric dimers showing a head-to-head arrangement which is stabilized by O—H⋯O hydrogen bonds. A weak C—H⋯O contact is also present.

In the title compound, C 11 H 14 O 4 , an intermediate for the synthesis of a new kind of estrogen receptor modulator, all non-H atoms lie on a common plane (r.m.s. deviation = 0.0472 Å ). All C-C bonds in the side chain are in a trans conformation, and the hydroxyl group is also trans to the methylene chain. In the crystal structure, molecules form centrosymmetric dimers showing a head-to-head arrangement which is stabilized by O-HÁ Á ÁO hydrogen bonds. A weak C-HÁ Á ÁO contact is also present.

Related literature
For the synthesis of 4-(3-methoxy-phenoxy)-butyric acid, see Tandon et al. (1990). For estrogen receptor modulators, see Lloyd et al. (2004). For a similar carboxylic acid, see: Smith et al. (1989).  Table 1 Hydrogen-bond geometry (Å , ).    et al., 2004). All non-H atoms of the title compound ( Fig. 1) lie in a common plane (r.m.s. deviation 0.0472 Å). All C-C bonds in the side chain are in a trans conformation, and the hydroxyl group is also trans to the methylene chain. In the crystal, the molecules form centrosymmetric dimers showing a head-to-head arrangement which is stabilized by O-H···O hydrogen bonds (Fig. 2). In addition to this classical hydrogen bond, there is weak C-H···O contact (Table 1).

Experimental
Synthesis of 4-(3-methoxy-phenoxy)-butyric acid ethyl ester (scheme 2): Cs 3 CO 3 (9.666 mmol, 3.149 g) was added to a solution of 3-methoxyphenol (8.055 mmol, 1.000 g) in acetone (20 ml) and the mixture was stirred for 5 min at r.t.. Ethyl-4-bromobutyrate (8.055 mmol, 1.571 g) was added and the reaction mixture was heated under reflux for 28 h. After cooling to r.t. the slurry was poured onto H 2 O/ice/HCl and the aqeous phase was extracted with CH 2 Cl 2 (4 x 25 ml). The combined organic layers were washed with H 2 O (3 x 25 ml), dried over MgSO 4 and the solvent was removed under reduced pressure to yield the crude product as a slightly yellow oil. The crude product was subjected to a column chromatography (eluent 100% CH 2 Cl 2 ), to obtain the pure product as a slightly yellow oil (1.486 g, 77%). and 1 M NaOH (20 ml) is added. The reaction mixture is stirred at r.t. for 1 h and is then poured into H 2 O/HCl (50 ml).
The aqeous phase is extracted with CH 2 Cl 2 (4 x 25 ml), and the combined organic layers are washed with H 2 O (2 x 30 ml), dried over MgSO 4 and the solvent is evaporated. The crude product is obtained as light yellow oil from which colourless crystals -suitable for X-Ray analysis -start to grow within 30 min. Purification of the crude product is conducted by column chromatography. The by-products are removed by elution with CH 2 Cl 2 . The desired product is then eluted with MeOH.

Refinement
H atoms bonded to C were refined with fixed individual displacement parameters [U(H) = 1.2 U eq (C) or U(H) = 1.5 U eq (C methyl )] using a riding model with C aromatic -H = 0.95 Å, C methyl -H = 0.98 Å, and C methylene -H = 0.99 Å. The methyl group was allowed to rotate but not to tip. the hydroxy H atom was freely refined. Fig. 1. Perspective view of the title compound with the atom numbering scheme; displacement ellipsoids are at the 50% probability level; H atoms are drawn as small spheres of arbitrary radii.    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.