1-Benzyl-4-piperidone → 4-(2-Fluoro-4-methoxyphenyl)-1-(phenylmethyl)-4-piperidinol

Participants

Reaction Conditions

Reaction Steps

To a stirred and cooled (0° C.) solution of 4-bromo-3-fluoroanisole (1 g; 4.88 mmol) in anhydrous THF (7 mL) was added isopropyl magnesium chloride (2.0M in THF; 2.22 mL; 4.43 mmol) dropwise. The reaction was stirred at room temperature for 30 min and then cooled to 0° C. 1-benzyl-4-piperidone (0.72 mL; 4.03 mmol) was added dropwise and the reaction was stirred at room temperature for 14 h. The reaction was quenched with saturated NH4Cl and partitioned between EtOAc (50 mL) and H2O (30 mL). The aqueous layer was extracted with EtOAc (3×50 mL) and the combined extracts were washed with brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography (0-50% EtOAc/hexanes gradient) to afford 1-benzyl-4-(2-fluoro-4-methoxyphenyl)piperidin-4-ol as a light orange solid. LCMS=315.9 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.38-7.31 (m, 5H), 7.28-7.24 (m, 1H), 6.66 (dd, J=8.7, 2.5 Hz, 1H), 6.61 (dd, J=14.4, 2.5 Hz, 1H), 3.79 (s, 3H), 3.56 (s, 2H), 2.77 (br d, J=10.6 Hz, 2H), 2.54-2.48 (m, 2H), 2.31-2.24 (m, 2H), 1.84 (d, J=12.3 Hz, 2H).

Provenance & Evidence