2-Bromo-6-methoxynaphthalene → 1-(6-Methoxy-2-naphthyl)-4-(trifluoromethyl)cyclohexanol

Participants

Reaction Conditions

Reaction Steps

To a cold (−78° C.) anhydrous solution of 2-methoxy-6-bromonaphthalene (1.52 g, 6.40 mmol) in THF (40 mL) was added n-BuLi (6.9 mL of a 2.5 M solution in hexanes, 6.9 mmol). The mixture was stirred at −78° C. under a nitrogen atmosphere for 15 min, then 4-(trifluoromethyl)cyclohexanone (0.88 g, 5.3 mmol) was added slowly to the reaction mixture. The bath was allowed to warm to room temperature and the reaction mixture was quenched with saturated NH4Cl (aq). The resultant mixture was extracted with EtOAc/hexanes. The organic layer was evaporated in vacuo and the crude residue was purified by flash chromatography on silica gel using gradient elution (0% to 20% EtOAc/hexanes, 150 mL; 20% to 35% EtOAc/hexanes, 204 mL; 35% to 75% EtOAc/hexanes, 381 mL) to provide Isomer A as the faster-eluting product and Isomer B as the slower-eluting product.

Provenance & Evidence