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

Temperature

-78 °C

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.

1. temperatureto warm to room temperature
2. customthe reaction mixture was quenched with saturated NH4Cl (aq)
3. extractionThe resultant mixture was extracted with EtOAc/hexanes
4. customThe organic layer was evaporated in vacuo
5. customthe 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)
6. customto provide Isomer A as the faster-eluting product and Isomer B as the slower-eluting product

ORD record

ord-75339baf5bdd468a94598a3f5736824f

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07989472B2