反应详情

NaH (60% in oil) (0.446 g, 11.16 mmol) was added to a solution of (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-hydroxy-4-(3′-vinylbiphenyl-3-yl)pyrrolidine-1,2-dicarboxylate (2.9 g, 6.20 mmol) and methyl iodide (0.698 mL, 11.16 mmol) at 0° C. in DMF and stirred at this temperature for 3 hrs. The reaction was then quenched with saturated NH4Cl solution and ether. The ether layer was washed with brine, dried, filtered and evaporated to give crude material. The crude material was purified by flash chromatography on the Biotage (5-45% EtOAc in hexanes) to give (2S,4R)-2-methyl 1-(2-(trimethylsilyl)ethyl) 4-methoxy-4-(3′-vinylbiphenyl-3-yl)pyrrolidine-1,2-dicarboxylate (2.3 g, 4.78 mmol, 77% yield) as a clear oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm −0.04-0.11 (m, 9H) 0.89-1.12 (m, 2H) 2.56 (dd, J=13.18, 8.91 Hz, 1H) 2.86 (t, J=12.67 Hz, 1H) 2.99 (d, J=3.01 Hz, 3H) 3.66-3.92 (m, 1H) 3.79 (d, J=7.03 Hz, 3H) 3.99-4.12 (m, 1H) 4.18-4.29 (m, 2H) 4.44-4.70 (m, 1H) 5.33 (d, J=10.79 Hz, 1H) 5.84 (d, J=16.82 Hz, 1H) 6.80 (dd, J=17.57, 11.04 Hz, 1H) 7.34 (d, J=7.53 Hz, 1H) 7.39-7.52 (m, 4H) 7.53-7.59 (m, 3H). LCMS: rt=2.49 min. [M+H]+=482; Phenomenex-Luna C-18 (5μ) (3.0×50 mm); Solvent A=10% acetonitrile—90% water—0.1% TFA, Solvent B=90% acetonitrile—10% water—0.1% TFA; gradient 0% to 100% solvent B over 2 min. and then hold for 1 min.; 4 mL/min; inj. vol.=5 uL; wavelength=220.

1. customThe reaction was then quenched with saturated NH4Cl solution and ether
2. washThe ether layer was washed with brine
3. customdried
4. filtrationfiltered
5. customevaporated
6. customto give crude material
7. customThe crude material was purified by flash chromatography on the Biotage (5-45% EtOAc in hexanes)