1-Fluoro-2-iodo-4-(methylsulfonyl)benzene → Tert-butyl(4-cyano-2-{[2-fluoro-5-(methylsulfonyl)phenyl]ethynyl}phenoxy)acetate

Participants

Reaction Conditions

Reaction Steps

A suspension of (4-cyano-2-ethynyl-phenoxy)-acetic acid tert-butyl ester (Intermediate 46; 200 mg; 0.78 mmol), 1-fluoro-2-iodo-4-(methylsulfonyl)benzene (Intermediate 77; 233 mg; 0.78 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloro palladium(II) (34 mg; 0.05 mmol) and cuprous iodide (9 mg; 0.05 mmol) was degassed during 2 minutes under nitrogen then anhydrous THF (3 ml) and TEA (215 μl; 1.55 mmol) were added and the reaction mixture was stirred at 70° C. for 16 hours. The solvents were removed under reduced pressure and the residue was purified by flash column chromatography (silica), eluting with cyclohexane containing increasing amounts of EtOAc to give the title compound (260 mg, 78%) as a yellow sticky solid.

Provenance & Evidence