Potassium Carbonate → Methyl 5'-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylthio)pyrimidin-5-yl]-2'-fluoro-4'-methoxy-2-methylbiphenyl-4-carboxylate

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Reaction Steps

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5-bromo-2-(methylthio)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 38, 158.7 mg, 0.299 mmol), methyl 2′-fluoro-4′-methoxy-2-methyl-5′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)biphenyl-4-carboxylate (144 mg, 0.359 mmol), K2CO3 (0-329 mL, 0.658 mmol), 1,1′-bis(diphenylphosphino) ferrocene-palladium dichloride dichloromethane adduct (36.7 mg, 0.045 mmol) and 1,4-dioxane (7 mL) were sealed in a microwave vessel and subjected to microwave irradiation at 140° C. for 20 min. LCMS trace of aliquot indicated completion of reaction. The reaction crude was combined with Crude-D1 and Crude-D2. The combined crude mixture was worked up with brine, extracted with EtOAc, dried (Na2SO4), filtered and evaporated to afford a dark mixture. The resulting dark mixture was purified by flash chromatography (SiO2, Biotage 40M cartridge). The column was eluted with a EtOAc/hexanes gradient mixture (0% to 30%). Related fractions were pooled and evaporated into 256 mg of yellow glass. TLC and LCMS trace indicated this yellow glass was not pure. The yellow glass was purified by preparative TLC (silica gel) developed with a EtOAc/hexanes mixture (30% EtOAc/hex, v/v) to give a yellow glass of 175 mg. This yellow glass was further purified by preparative TLC (silica gel, EtOAc/CH2Cl2, 2.5%, v/v) to give a yellow glass as the titled compound. LCMS calc.=723.16; found=724.03 (M+H)+.

Provenance & Evidence