5-Bromo-2-methoxypyridine → 1-(6-Methoxypyridin-3-yl)-4-(trifluoromethyl)cyclohexanol

Participants

Reaction Conditions

Reaction Steps

n-Butyllithium (3 mL of a 2.5 M solution in hexanes, 7.5 mmol) was added dropwise to 5-bromo-2-methoxy pyridine (6.0 mmol, 0.78 mL) in 40 mL of THF cooled in a dry ice/acetone bath. After aging for 15 min, 4-trifluoromethylcyclohexanone (6.0 mmol, 1 g) was added and the reaction mixture was allowed to slowly warm to 0° C. over 2 h. The reaction was cooled in a dry ice/acetone bath and the reaction was quenched by addition of sat. ammonium chloride (aq), then saturated sodium bicarbonate (aq). The reaction mixture was extracted with hexanes/EtOAc. The organic phase was concentrated and the resultant residue was purified by flash chromatography on silica gel using a step gradient of 4:1, 2:1 and 1:1 (v/v) EtOAc/hexanes to give the title compound as a mixture of isomers. LC-MS (ESI): m/z=276.2 [M+1]+.

Provenance & Evidence