反应详情

methyl 2′,4′-difluoro-5′-iodo-2-methylbiphenyl-4-carboxylate (100 mg, 0.26 mmol, dissolved in 1 mL ethanol), (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 (INTERMEDIATE 9, 185 mg, 0.31 mmol, dissolved in 2.2 mL 1,4-dioxane), sodium carbonate (258 μL, aq., 2M, 0.516 mmol) and 1,1′-bis(diphenylphosphino) ferrocene-palladium dichloride dichloromethane adduct (42 mg, 0.05 mmol) were heated in an 80° C. oil bath for 2 hours. LCMS trace of reaction aliquot indicated completion of reaction. Reaction crude was dried/Na2SO4 and then deposited on 2 prep-TLC plates (SiO2). The plates were developed by a 20% EtOAc/hexanes mixture to afford a clear glass. The glass was further purified by reverse-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting w/a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture. Corresponding fractions were pooled & evaporated in vacuo to afford a colorless glass. This glass was dissolved in DCM and washed with water. Organic extracts were combined, dried/Na2SO4, filtered and evaporated to afford the title compound. LCMS (ESI) calc.=731.15; found=732.06 (M+1)+.

1. customLCMS trace of reaction
2. customcompletion of reaction
3. customReaction crude
4. dry with materialwas dried/Na2SO4
5. customto afford a clear glass
6. customThe glass was further purified by reverse-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm)
7. washeluting w/a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture
8. customevaporated in vacuo
9. customto afford a colorless glass
10. washwashed with water
11. dry with materialdried/Na2SO4
12. filtrationfiltered
13. customevaporated