tert-Butanol → HCID 66970921, compound

Participants

Reaction Steps

1-((1S,2R,4R)-bicyclo[2.2.1]heptan-2-yl)-4-(2-methoxyphenyl)piperidine hydrochloride (397, 64 mg, 0.20 mmol) was suspended in nitrobenzene (1.0 mL) and treated with 1.0 eq tert-butanol (15 mg), followed by 3.0 eq of aluminum trichloride in nitrobenzene (600 μL 1.0 M solution, 0.60 mmol). The reaction was stirred at room temperature for 2 hours, then quenched with 1.0 N HCl (5.0 mL). The aqueous layer was separated, basified with 1.0 N NaOH (pH 12) and extracted with dichloromethane (10 mL). The extract was dried (Na2SO4), filtered, concentrated in vacuo and dissolved in methanol:acetonitrile (1.0 mL, 1:1 v/v). The solution was filtered (Whatman 0.2 μm PTFE) and subjected to reverse-phase HPLC purification (5-50% CH3CN/0.08% TFA) to yield [1-((1S,2R,4R)-bicyclo[2.2.1]heptan-2-yl)-4-(5-tert-butyl-2-methoxy-phenyl)piperidine] (compound no. 325) as the TFA salt. LC/MS (RP-C18, 10-99% CH3CN/0.05% TFA gradient over 5 min) m/z 342.2 [M+H]+, retention time 2.70 min.

Provenance & Evidence