Triphenylarsine → 5(R)-isoxazol-3-yloxymethyl-3-(4-{8-tert-butyloxycarbonyl-8-azabicyclo[3.2.1]oct-2-ene-3-yl}-3-fluorophenyl)oxazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

Tris(dibenzylideneacetone) dipalladium(0) (0.19 g, 0.208 mmol), triphenylarsine (0.13 g, 0.425 mmol) and lithium chloride (0.265 g, 6.31 mmol) were added to a stirred solution of 5(R)-isoxazol-3-yloxymethyl-3-(3-fluoro-4-iodophenyl)oxazolidin-2-one (prepared by analogy to reference Example 28) (0.85 g, 2.1 mmol) in degassed DMF (35 ml) under nitrogen. After 5 minutes, a solution of 8-tert-butyloxycarbonyl-3-trimethylstannyl-8-azabicyclo[3.2.1]oct-2-ene (GB 2298647; 0.78 g, 2.1 mmol) in DMF (4 ml) was added and the mixture was heated at 60° C. for 18 hours. A solution of 2M potassium fluoride (30 ml) was added and the mixture stirred for 40 minutes. Solvent was evaporated and the residue partitioned between water and EtOAc. The aqueous layer was extracted twice with EtOAc and the combined extracts dried (Na2SO4) and evaporated. The residue was purified by column chromatography, eluting with a gradient of dichloromethane-5% MeOH/dichloromethane to give 5(R)-isoxazol-3-yloxymethyl-3-(4-{8-tert-butyloxycarbonyl-8-azabicyclo[3.2.1]oct-2-ene-3-yl }-3-fluorophenyl)oxazolidin-2-one as an oil of 85% purity [hplc](0.97 g, 81%). MS: 486 (MH+).

Provenance & Evidence