HCID 19348477, compound → Methyl 3-(2,4-dimethoxy-5-propionylphenyl)octanoate

Participants

Reaction Steps

A solution of 644 mg (2.0 mmol) of methyl 3-(2,4-dimethoxy-5-formylphenyl)octanoate [prepared as described in Preparation 32(ii)] in 10 ml of tetrahydrofuran was added dropwise over a period of 5 minutes to a solution of 1.2 ml (2.2 mmol) of a 1.8M solution of ethylmagnesium iodide in diethyl ether diluted with 20 ml of tetrahydrofuran, whilst ice-cooling, and the resulting mixture was stirred at the same temperature for 40 minutes. The reaction was then terminated by the addition of a saturated aqueous solution of ammonium chloride, and the resulting mixture was extracted with a mixture of ethyl acetate and hexane. The extract was washed several times with water and once with a saturated aqueous solution of sodium chloride, after which it was dried over anhydrous sodium sulfate. The solvent was then removed by distillation under reduced pressure, giving the title compound as a crude product. This product was dissolved in 40 ml of methylene chloride, and 3.48 g of manganese dioxide were added to the resulting solution. The resulting mixture was stirred for 1 hour, after which a further 3.48 g of manganese dioxide were added. The mixture was then stirred for 12 hours, and then a further 1.72 g of manganese dioxide [8.68 g (99.8 mmol) in total] were added to the mixture, which was then stirred for 8 hours. At the end of this time, the reaction mixture was filtered using a Celite (trade mark) filter aid, and the filtrate was concentrated by evaporation under reduced pressure. The concentrate was triturated with hexane to give approximately pure crystals of the title compound. The compound was further purified by column chromatography through 10 g of silica gel, using a gradient elution method, with mixtures of hexane and ethyl acetate ranging from 5:1 to 3:1 by volume as the eluent, to give 416 mg (yield 59%) of the desired propionyl derivative, melting at 75.5°-77.5° C. (from hexane).

Provenance & Evidence