Iodine → 1-(Benzo[b]thiophen-5-yl)-3-methylbutan-1-one

Participants

Reaction Steps

A few drops of a solution of 5-bromobenzo[b]thiophene (2 g; prepared in a manner similar to that described in Example 21) in tetrahydrofuran (10 ml) was added under nitrogen to a mixture of magnesium turnings (0.24 g), tetrahydrofuran (2 ml) and a few small crystals of iodine, heat was applied to initiate the reaction, then the remainder of the bromobenzo[b]thiophene solution was added at reflux temperature over 10 minutes. When the addition was complete, the mixture was heated under reflux for 1 hour, then a solution of N-methoxy-N,3-dimethylbutyramide (1.43 g) in tetrahydrofuran (10 ml) was added. The mixture was heated under reflux for 1 hour, cooled to ambient temperature, then quenched by the addition of 2M hydrochloric acid (25 ml) and stirred at ambient temperature for 5 minutes. The majority of the tetrahydrofuran was removed in vacuo, then water (25 ml) was added to the residue and the product was extracted into ethyl acetate (2×25 ml). The extracts were washed with water (25 ml) and saturated aqueous sodium chloride solution (25 ml), dried (MgSO4) and the solvent removed in vacuo. The residue was purified by flash chromatography over silica using petroleum ether (b.p. 60-80° C.) followed by a 95:5 mixture of petroleum ether (b.p. 60-80° C.) and ethyl acetate as eluants. Appropriate fractions were combined and the solvents removed in vacuo to give 1-(benzo[b]thiophen-5-yl)-3-methylbutan-1-one (1.25 g) as an off-white solid which was used without further purification.

Provenance & Evidence