Microwave-Assisted Azacyclonol Synthesis

Azacyclonol (1 equivalent), ketone (1 equivalent), potassium carbonate (5 equivalents), a catalytic amount of potassium iodide and 18-crown-6 were stirred in dry acetonitrile (4 mL) in the microwave (CEM Discover) at 150 Watt, 6.5 bar, 175 °C for 45 min or (MultiSYNTH) at 100 Watt, 140 °C, 3 h (2g, 2h, 2t, 2u, 2v, 2w) or at 50 Watt, 100 °C, 5 min (8a). The microwave assisted reactions were performed in a continuous air stream cooled closed vessel. Reaction temperature was monitored via an IR sensor in both microwave ovens and an additional fiber optic component in case of the MultiSYNTH. After filtering off the remaining precipitate the solvent was removed. The impurities could not be removed completely by flash chromatography (6/1 ethyl acetate/n-hexane + 3 % NEt₃), so preparative HPLC (isocratic 70/30 MeOH/H₂O) was performed and the pure product isolated.