[Synthesis]
General procedure for the synthesis of 6-bromospiro[chroman-2,4'-piperidin]-4-one hydrochloride from 2-hydroxy-5-bromoacetophenone (6.0 g, 0.027 mol) and N-tert-butyloxycarbonyl-4-piperidone (5.55 g, 0.027 mol): firstly, 2-hydroxy-5-bromoacetophenone was mixed with pyrrolidine (2.7 mL, 0.033 mol) in methanol ( 48 mL) in a sealed flask and stirred at 25 °C for 20 min. Subsequently, N-tert-butoxycarbonyl-4-piperidone was added to the reaction mixture and the mixture was heated to 80 °C and kept for 16 hours. After completion of the reaction, the mixture was concentrated under vacuum and the residue was dissolved in dichloromethane (50 mL) and cooled to 15 °C. Next, it was treated with 4 M hydrochloric acid-dioxane solution (30 mL) and stirred at room temperature for 16 hours. At the end of the reaction, the solid product was collected by filtration and washed with dichloromethane to afford 6-bromospiro[chroman-2,4'-piperidin]-4-one hydrochloride as a cream colored solid (8.92 g, 96% yield). The product was confirmed by 1H NMR (400 MHz, CD3OD): δ 7.93 (d, J=2.5 Hz, 1H), 7.71 (dd, J=8.9,2.6 Hz, 1H), 7.11 (d, J=9.0 Hz, 1H), 3.32-3.41 (m, 4H), 2.90 (s, 2H), 2.23-2.36 (m, 2H) , 1.87-2.05 (m, 2H). Mass spectrometry analysis (ESI) showed the molecular ion peak m/z 297 [M+H]+, which corresponds to the theoretically calculated value (C13H14BrNO2+H)+ 297.02. |