Cesium carbonate → Methyl 6-amino-3-[2-(tert-butyldimethylsilanyloxymethyl)-4-fluoro-5-trimethylsilanylfuran-3-yl]-2-hydroxybenzoate

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-(tert-butyldimethylsilanyloxymethyl)-4-fluoro-5-trimethylsilanylfuran-3-yl-boronic acid (Intermediate 103, 6.0 g), methyl 6-amino-3-bromo-2-hydroxybenzoate (prepared according to Wang et al, Bioorg Med Chem Lett 2007 17 2817, 4.27 g), tris-(dibenzylideneacetone)dipalladium (0.793 g), tri-tert-butylphosphonium tetrafluoroborate (0.502 g) and cesium carbonate (16.94 g) in dioxane (96 mL) and water (12 mL) was heated at 63° C., under an atmosphere of nitrogen for 90 minutes. The mixture was cooled and diluted with ethyl acetate, washed with water, dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 0-20%. The resultant product was re-purified by chromatography on silica, eluting with a mixture of DCM and cyclohexane, with a gradient of 0-100% to give methyl 6-amino-3-[2-(tert-butyldimethylsilanyloxymethyl)-4-fluoro-5-trimethylsilanylfuran-3-yl]-2-hydroxybenzoate (3.86 g) as a yellow oil which crystallised with scratching to give an off-white solid.

Provenance & Evidence