3-Hydroxy-1-(4-methoxybenzyl)piperidin-2-one

The title compound, C13H17NO3, adopts a conformation in which the aromatic ring and the mean plane of the piperidine ring are almost perpendicular to each other [dihedral angle = 79.25 (6)°]. The presence of the carbonyl group alters the conformation of the piperidine ring from a chair to a twisted half-chair conformation. In the crystal, pairs of strong O—H⋯O hydrogen bonds link the molecules into inversion dimers. Weak C—H⋯O interactions extend the hydrogen-bonding network into three dimensions.


Comment
The title piperidinone was prepared as an early intermediate for the total synthesis of febrifugine, a quinazoline alkaloid with potent antimalarial activity (Murata et al., 1998). Ongoing investigations in our laboratories have made use of similar lactams for the synthesis of febrifugine analogues (Michael et al., 2006). It should be noted that, although the 3hydroxy substituent was introduced by attempted asymmetric hydroxylation of the enolate of 1-(4-methoxybenzyl)piperidin-2-one with (+)-camphorsulfonyloxaziridine (Davis et al., 1990), partial racemization occurred; the crystals selected for analysis proved to be racemic.
The title organic compound (Fig. 1) adopts a conformation in which the aromatic ring and the piperidine ring are almost perpendicular to each other. Ring puckering analysis, as implemented in PLATON (Spek, 2009), indicates that the piperidine ring adopts a twisted half-chair conformation owing to the presence of the carbonyl group (Boeyens, 1978).
Several hydrogen bonds exist in the structure (Table 1)

Experimental
To a solution of lithium hexamethyldisilazide, prepared from n-butyllithium (1.6 M in hexane, 1.83 ml, 2.93 mmol) and hexamethyldisilazane (0.63 ml) in THF (10 ml) at -70 °C was added a solution of 1-(4-methoxybenzyl)piperidin-2-one (322 mg, 1.47 mmol) in THF (20 ml). The solution was stirred at this temperature for 1 h, after which a solution of (+)camphorsulfonyloxaziridine (0.67 g, 2.9 mmol) in THF (20 ml) was added dropwise. Stirring was maintained for a further 16 h at temperatures kept between -70 and -60 °C. The reaction was quenched by addition of saturated aqueous ammonium chloride solution (10 ml) and allowed to warm to ambient temperature. The organic components were extracted with dichloromethane (4 × 15 ml), the combined organic layers were washed with brine (20 ml), dried over MgSO 4 , and concentrated in vacuo. Purification by column chromatography on silica gel with hexane-ethyl acetate mixtures (9:1 to 1:1 v/v) yielded the title compound, which was recrystallized from hexane-ethyl acetate to yield the product as irregularly shaped colourless crystals (261 mg, 75%), m.p. 347-349 K.

Refinement
All H atoms attached to C atoms were positioned geometrically, and allowed to ride on their parent atoms, with C-H bond lengths of 0.95 Å (Ar-H), 1.0 (CH), 0.99 Å (CH 2 ) or 0.98 Å (CH 3 ), and isotropic displacement parameters set to 1.2 (CH and CH 2 ) or 1.5 times (CH 3 ) the U eq of the parent atom. The alcohol H atom (H2) was located from the difference map and refined freely with isotropic displacement parameter set to 1.5 times the U eq of the parent atom O2.