Methyl iodide → 1-[5-(Methoxymethyl)isoxazol-3-yl]ethanone

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-[5-(hydroxymethyl)-1,2-oxazol-3-yl]ethanone (1.00 g, 7.09 mmol) in dry THF (20 mL) under an atmosphere of nitrogen was introduced cesium carbonate (2.31 g, 7.09 mmol) and methyl iodide (5.03 g, 35.43 mmol). The reaction mixture was warmed to 60° C. for 16 hr, cooled to RT and the solids removed by filtration. The filtrate was re-treated with additional cesium carbonate (4.31 g, 13.23 mmol) and methyl iodide (9.59 g, 67.58 mmol) and warmed to 60° C. for 34 hr. After cooling to RT, the reaction mixture was filtered, concentrated in vacuo and the residue re-dissolved in EtOAc (50 mL). The EtOAc solution was washed with water (25 mL), brine (25 mL), dried (Na2SO4) and filtered. After concentrating the filtrate in vacuo, the residual oil was purified by silica gel flash column chromatography (95:5-50:50 gradient of heptane/EtOAc) to furnish the title compound as a colorless oil: 1H NMR (500 MHz, CDCl3) delta 2.66 (3H, s), 3.44 (3H, s), 4.59 (2H, s), 6.64 (1H, s).

Provenance & Evidence