Cesium carbonate → tert-Butyl 4-(2-(ethoxycarbonyl)benzofuran-4-yl)piperazine-1-carboxylate

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Reaction Steps

Ethyl 4-bromobenzofuran-2-carboxylate (prepared in analogy with ethyl 4-chlorobenzofuran-2-carboxylate, (Example 1b), starting from 2-bromo-6-hydroxy-benzaldehyde) (7.7 g, 29 mmol), tert-butyl piperazine-1-carboxylate (5.33 g, 28.6 mmol), tris(dibenzylideneacetone)dipalladium(0) (1.31 g, 1.43 mmol), 2-dicyclohexylphosphino-2′,4′,6′-tri-iso-propyl-1,1′-biphenyl (1.36 g, 2.86 mmol) and cesium carbonate (12.1 g, 37.2 mmol) in dioxane (40 mL) was heated under argon to +95° C. overnight. The mixture was allowed to cool, diluted with ethyl acetate and filtered through a pad of Celite. The filtrate was collected and the solvent was removed by rotary evaporation. The crude product was added to a silica gel column and eluted with 0-50% ethyl acetate in heptane. The collected fractions were combined and the solvent was removed to give the title compound, which was used in the subsequent step ii). Yield: 4.92 g, 46%. MS m/z 375.8 [M+H]+.

Provenance & Evidence