2'-Hydroxyacetophenone → 1'-Benzoylspiro[chroman-2,4'-piperidin]-4-one

Participants

Reaction Steps

A solution of 2′-hydroxyacetophenone (5, 5.88 mL, 48.85 mmol), 1-benzoyl-4-piperidone (6, 10 g, 49 mmol), and pyrrolidine (4.1 mL, 49 mmol) in 55 mL of methanol was heated in an oil bath at 65° C. After ˜18 hours the oil bath was removed and the solution was allowed to cool to room temperature. Additional 1-benzoyl-4-piperidone (6, 100 mg, 0.5 mmol) was added and heating at 65° C. was resumed. After an additional ˜2.5 hours the oil bath was removed and the solution was allowed to cool to room temperature. This mixture was concentrated under reduced pressure on a rotary evaporator followed by high vacuum to give a viscous, orange oil. This oil was triturated with diethyl ether to provide a solid that was collected by vacuum filtration, washed with diethyl ether, and dried in vacuo at room temperature to afford 1′-benzoylspiro[chroman-2,4′-piperidin]-4-one (7) as an off-white solid (14.72 g, 93.8% yield). The filtrate was evaporated to dryness, triturated with diethyl ether, filtered, washed with diethyl ether, and dried in vacuo at room temperature to afford additional compound 7 as a pale tan solid (0.54 g, 3.7% yield). Both samples were homogeneous by TLC (silica gel, 1.5% methanol in dichloromethane, UV visualization; Rf (7)=0.15−0.2).

Provenance & Evidence