Cesium carbonate → (S)-2-[4-(2-fluoro-3-pyrrolidin-1-yl-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

To a mixture of (S)-2-[4-(3-bromo-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid ethyl ester (prepared as in Example 128, 0.300 g, 0.72 mmol), palladium(II) acetate (0.023 g, 0.10 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.124 g, 0.20 mmol), and cesium carbonate (0.650 g, 1.99 mmol) in 1,4-dioxane (10 mL) was added pyrrolidine (0.103 g, 1.45 mmol) and the resulting mixture heated to 100° C. in a sealed tube under argon for 6 h. The resulting mixture was taken up in ethyl acetate and water, separated and the organic phase washed with a saturated sodium chloride solution and concentrated. The residue was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 50 g, 5% to 40% ethyl acetate/hexanes) which afforded (S)-2-[4-(2-fluoro-3-pyrrolidin-1-yl-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid ethyl ester (0.120, 41%) as an oil.

Provenance & Evidence