反应详情

A mixture of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-prop-2-yn-1-yl-1,3-oxazolidin-2-one (100 mg, 0.285 mmol), 1-bromo-4-fluoro-5-isopropyl-2-methoxybenzene (27.4 wt % in toluene, 233 mg, 0.259 mmol), bis(triphenylphosphine)palladium dichloride (18.2 mg, 0.0259 mmol), copper (I) iodide (4.9 mg, 0.0259 mmol), triphenylphosphine (13.6 mg, 0.0518 mmol), and diethylamine (283 mg, 406 μL, 3.88 mmol) in dry DMF (0.5 mL) was degassed and subjected to microwave irradiation (120° C., 60 min). The reaction mixture was diluted with 0.1N HCl (10 mL) and extracted with EtOAc (3×20 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 12×160 mm, 0-30% EtOAc in hexanes gradient) to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)prop-2-yn-1-yl]-4-methyl-1,3-oxazolidin-2-one. Rf=0.38 (20% EtOAc/hexanes). LCMS calc.=518.2; found=518.2 (M+1)+. 1H NMR (500 MHz, CDCl3): δ 7.89 (s, 1H); 7.78 (s, 2H); 7.26 (d, J=8.4 Hz, 1H); 6.56 (d, J=12.0 Hz, 1H); 5.76 (d, J=8.3 Hz, 1H); 4.70 (d, J=17.8 Hz, 1H); 4.53-4.47 (m, 1H); 4.08 (d, J=17.8 Hz, 1H); 3.82 (s, 3H); 3.17-3.09 (m, 1H); 1.22 (d, J=6.9 Hz, 6H); 0.90 (d, J=6.5 Hz, 3H).

1. customwas degassed
2. customsubjected to microwave irradiation (120° C., 60 min)
3. additionThe reaction mixture was diluted with 0.1N HCl (10 mL)
4. extractionextracted with EtOAc (3×20 mL)
5. dry with materialThe combined extracts were dried (Na2SO4)
6. concentrationconcentrated in vacuo
7. customto give the crude product
8. customThis was purified by flash chromatography (Si, 12×160 mm, 0-30% EtOAc in hexanes gradient)