o-Anisalacetone → 5-(2-Methoxyphenyl)-1,3-cyclohexanedione

Participants

Reaction Steps

To a stirred solution of NaOEt (21% in EtOH) (9.8 ml, 26.5 mmol) under nitrogen was added diethylmalonate (3.7 ml, 24.3 mmol). The reaction mixture was stirred at ambient temperature for 20 min. 4-(2-methoxy-phenyl)-but-3-en-2-one (3.89 g, 22.1 mmol), Stage 1, was dissolved in ethanol (20 ml) and added to the reaction mixture, which was stirred at reflux and monitored by LC-MS until 4-(2-methoxy-phenyl)-but-3-en-2-one was consumed. The reaction mixture was cooled to ambient temperature. An aqueous solution of sodium hydroxide (2M, 10 ml) was added to the reaction mixture, which was heated at 80° C. for 1.5 h. Excess ethanol was removed by evaporation and the aqueous phase was washed with toluene (20 ml). The aqueous phase was acidified with conc. HCl (5 ml) and the reaction mixture was refluxed for 1 h and left to cool to ambient temperature. The compound was extracted with ethyl acetate (2×30 ml), dried with MgSO4 and filtered. The solvent was removed under reduced pressure. The title compound was purified by column chromatography eluting with ethyl acetate/heptane (1/1) to give a beige solid.

Provenance & Evidence