Nitrogen → 8-[4-(6-(2,5-Dimethylpyrrolyl)-pyridin-2-yl)-phenyl]-3-benzyl-3-aza-bicyclo[3.2.1]octan-8-ol

Participants

Reaction Conditions

Reaction Steps

To a 125 mL 3-necked round-bottomed flask equipped with septum and N2 inlet were added 1.86 g (5.70 mmol) 6-bromo-2-(2,5-dimethylpyrrolyl)-pyridine and 40 mL dry tetrahydrofuran. The solution was cooled to −60° C., and 2.73 mL (6.84 mmol) of a 2.5M solution of butyl lithium in hexane was added dropwise and the solution stirred 10 min at −60° C. Then a solution of 1.47 g (6.84 mmol) 3-benyl-3-aza-bicyclo[3.2.1]octan-8-one in 15 mL dry tetrahydrofuran was added dropwise, and the reaction stirred at −60° C. for 10 minutes, and then at room temperature for 3 hours. The reaction was quenched with aqueous ammonium chloride solution and taken up in ethyl acetate. The organic layer was separated and washed with more aqueous ammonium chloride solution and brine, dried over sodium sulfate, and evaporated. The residue was chromatographed on silica gel using methanol and methylene chloride to afford 413 mg (16%) of a yellow oil which solidified, mp 58-68° C.

Provenance & Evidence