反应详情

Methyl 3′-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-chloropyridin-3-yl]-4′-methoxy-2-methylbiphenyl-4-carboxylate (120 mg, 0.966 mmol), isopropenylboronic acid (74.4 mg, 0.865 mmol), 1,1′-bis(di-tert-butylphosphino) ferrocene palladium dichloride (23.5 mg, 20%), aqueous potassium carbonate (1.21 mL, 1M, 1.21 mmol) and THF (1.2 mL) were heated in an 80° C. oil bath for 1 h and 25 min. Volatiles were then removed from the crude mixture under reduced pressure. The pot residue was treated with water followed by EtOAc extraction. The combined extracts were dried over Na2SO4 followed by filtration and concentration to afford a dark colored oil. The resulting oil was purified by a reversed-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting with a MeCN (0.1% TPA, v/v)/H2O (0.1% TFA, v/v) gradient mixture. Related fractions were pooled and evaporated in vacuo to afford a light yellow oil. The oil was dissolved with CH2Cl2 and then washed with NaHCO3 (sat. aq.). The organic layer was separated and back washed with water, separated and dried over Na2SO4, filtered and concentrated in vacuo to afford methyl 3′-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-isopropenylpyridin-3-yl]-4′-methoxy-2-methylbiphenyl-4-carboxylate, as a light yellow glass. LCMS calc.=698.22; found 699.23 (M+1).

1. custom25 min
2. customVolatiles were then removed from the crude mixture under reduced pressure
3. additionThe pot residue was treated with water
4. extractionfollowed by EtOAc extraction
5. dry with materialThe combined extracts were dried over Na2SO4
6. filtrationfollowed by filtration and concentration
7. customto afford a dark colored oil
8. customThe resulting oil was purified by a reversed-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm)
9. washeluting with a MeCN (0.1% TPA, v/v)/H2O (0.1% TFA, v/v) gradient mixture
10. customevaporated in vacuo
11. customto afford a light yellow oil
12. washwashed with NaHCO3 (sat. aq.)
13. customThe organic layer was separated
14. washback washed with water
15. customseparated
16. dry with materialdried over Na2SO4
17. filtrationfiltered
18. concentrationconcentrated in vacuo