反应详情

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 9) (107.0 mg, 0.207 mmol) and 2-[4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-methylpropan-1-ol (64 mg, 0.207 mmol) in THF (2.3 mL) was added aqueous potassium carbonate (1.6 mL of a 1M solution, 1.6 mmol). The mixture was degassed with nitrogen. While stirring the reaction vigorously at room temperature, 1,1-bis(di-t-butylphosphino)ferrocene palladium chloride (6.7 mg, 0.01 mmol) was added. The reaction was stirred vigorously at room temperature for 15 min, and then diluted with EtOAc (50 mL). The organics were washed with water and brine (15 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel (5 to 50% EtOAc/hexanes) afforded impure product, which was repurified with 1:1:1 CH2Cl2:hexanes:Et2O on silica gel to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({6-chloro-3-[5-(2-hydroxy-1,1-dimethylethyl)-2-methoxyphenyl]pyridin-2-yl}methyl)-4-methyl-1,3-oxazolidin-2-one. Rf=0.29 (40% EtOAc/hexanes). LCMS=616.9 (M+1)+. 1H NMR (CDCl3, 500 MHz, rotamers present) δ 6.94-7.85 (m, 8H), 5.40-5.55 (m, 1H), 4.81-5.08 (m, 1H), 3.54-4.36 (m, 7H), 1.95-2.59 (m, 1H), 1.30-1.34 (m, 6H), 0.62-0.74 (m, 3H).

1. customThe mixture was degassed with nitrogen
2. customthe reaction vigorously at room temperature
3. stirringThe reaction was stirred vigorously at room temperature for 15 min
4. washThe organics were washed with water and brine (15 mL each)
5. dry with materialThe organic layer was dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customPurification of the residue by flash chromatography on silica gel (5 to 50% EtOAc/hexanes)
9. customafforded impure product, which
10. customwas repurified with 1:1:1 CH2Cl2