3-Quinuclidinone → HCID 10206384, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of 280 mg of 2-(4-bromophenyl)-6-methyl-1,3,6,2-dioxyazaborocane (Production Example 14) and 10 ml of tetrahydrofuran was added dropwise 2 ml of a 1 M cyclohexane-hexane solution of sec-butyllithium under nitrogen atmosphere while cooling in a liquid nitrogen-tetrahydrofuran bath at −90° C., followed by stirring as it was for 40 minutes. Then, a solution of 130 mg of 3-quinuclidinone in 1 ml of tetrahydrofuran was added to the mixture, the liquid nitrogen-tetrahydrofuran bath was removed and the mixture was stirred at room temperature for 30 minutes. 1 ml of an aqueous ammonium chloride solution was added to the reaction mixture, followed by evaporating. To the residue were added 5 ml of methanol, 2 ml of a 5 Maqueous solution of potassium carbonate, 220 mg of 2-benzyl-3-iodo-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]pyridine hydrochloride and 5 ml of diethoxymethane, followed by heating under stirring under nitrogen atmosphere in an oil bath at 60° C. for 3 hours. The reaction mixture was extracted with ethyl acetate-water, and the organic layer was washed with water and brine, dried over anhydrous magnesium sulfate and then evaporated. The residue was subjected to column chromatography using NH-silica gel with 50% ethyl acetate-hexane and 0–5% methanol-ethyl acetate, to give 60 mg of the title compound.

Provenance & Evidence