1-Methyl-4-piperidone → 5-Chloro-2-(4-hydroxy-1-methylpiperidin-4-yl)benzothiophene

Participants

Reaction Conditions

Reaction Steps

A solution of 0.300 gm (1.78 mMol) 5-chlorobenzothiophene in 20 mL tetrahydrofuran was cooled to -78° C. To the cooled solution was then added 1.27 mL (1.78 mMol) n-butyllithium (1.2M in tetrahydrofuran) and the reaction mixture stirred for 1 hour after the addition was complete. To this solution was added 0.218 mL (1.78 mMol) 1-methyl-4-piperidone and the reaction mixture was allowed to warm to 0° C. The reaction mixture was quenched with saturated aqueous sodium bicarbonate and partitioned by the addition of hexane/diethyl ether. The organic phase was washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure to provide 0.34 gm of a tan solid. This residue was subjected to silica gel chromatography, eluting with chloroform containing 5% methanol. Fractions containing product were combined and concentrated under reduced pressure to provide 0.34 gm (68%) of the title compound as an off-white solid.

Provenance & Evidence