Potassium Hydroxide → benzyl 5-[2'-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-methoxy-4'-(trifluoromethyl)biphenyl-3-yl]-6-methylpyridine-2-carboxylate

Participants

Reaction Steps

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one-methane (385 mg, 0.644 mmol) (INTERMEDIATE 9), benzyl 5-(3-iodo-4-methoxyphenyl)-6-methylpyridine-2-carboxylate (148 mg, 0.322 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride (71 mg, 0.097 mmol), aqueous potassium hydroxide (215 μL, 3M, 0.645 mmol) and 1,4-dioxane (2 mL) were charged into a tube. The vessel was purged with nitrogen and then sealed. The reaction mixture was irradiated by microwave at 120° C. for 20 minutes then at 140° C. for 30 minutes. The reaction mixture was treated with water followed by extraction with ethyl acetate. The combined extracts were dried over Na2SO4 followed by filtration and concentration in vacuo to afford a dark oil. This oil was purified by preparative TLC on SiO2 (eluted with 45% ethyl acetate in hexanes) to afford a dark oil. The resulting oil was further purified by reverse-phase preparative-HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting with a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture. The appropriate fractions were pooled and evaporated into a dark oil. This oil treated with sodium bicarbonate aqueous solution (sat.) followed by ethyl acetate extractions. The combined extracts were dried over Na2SO4 followed by filtration and concentration in vacuo to afford a dark oil. The oil still contained some baseline impurities. The resulting oil was again purified by preparative TLC on SiO2 (eluted with 50% ethyl acetate in hexanes) to afford benzyl 5-[2′-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-methoxy-4′-(trifluoromethyl)biphenyl-3-yl]-6-methylpyridine-2-carboxylate. LCMS calc.=802.21; found=803.21 (M+1)+.

Provenance & Evidence