Acetic Acid → (1R*,2R*,5R*)-2-{[3,5-Bis(trifluoromethyl)phenyl]methoxy}-1-(4-fluorophenyl)-8-azabicyclo[3.2.1]octane

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Reaction Steps

(1R*,2R*,5R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-(4-fluorophenyl)-8-azabicyclo[3.2.1]octane (Example 17; 1.51 g, 2.81 mmol) was dissolved in ethyl acetate (20 ml) and glacial acetic acid (2 ml) and 10% palladium hydroxide (200 mg) added and hydrogenated at 45 psi overnight. The reaction mixture was filtered then concentrated in vacuo. The oil was basified (4N sodium hydroxide) and the solution extracted with ethyl acetate (×3). The organics were dried (MgSO4) and concentrated in vacuo. The mixture was purified by flash column chromatography [7.5% methanol in dichloromethane] to give a yellow oil which solidified on standing to give the title compound (506 mg, 40%). The hydrochloride salt was made by adding 1 equivalent of 1N hydrogen chloride in diethyl ether to the title compound (31 mg, 0.06 mmol). A white solid formed which was triturated in diethyl ether and filtered then dried at 60° C. in vacuo (29.8 mg, 89%).

Provenance & Evidence