反应详情

温度

0 °C

To a 0° C. solution of 0.6 g (1.25 mmol) ethyl(2-{(tert-butoxycarbonyl)[2,2-difluoro-2-(1-oxido-2-pyridinyl)ethyl]amino}-5-chloro-3-fluoro-4-pyridinyl)acetate 1-7 in 20 mL EtOAc was passed a steady stream of HCl gas for 10 min, then the reaction mixture was allowed to stir at 0° C. for 1 hr. A stream of N2 gas was then passed through the mixture for 5 min, and the mixture poured into 200 mL EtOAc/50 mL 2M NaOH/7 mL conc NaOH and the layers mixed and separated. The aqueous, layer was back extracted with 50 mL EtOAc and the combined organic layers washed with 150 mL water, and brine, then dried over Na2SO4, filtered, concentrated, to give ethyl(5-chloro-2-{[2,2-difluoro-2-(1-oxido-2-pyridinyl)ethyl]amino}-3-fluoro-4-pyridinyl)acetate 1-8 which was used without further purification. 1H NMR (400 mHz, CDCl3) δ8.28 (br d, 1H, J=6.41 Hz); 7.81 (s, 1H); 7.62 (dd, 1H, J=8.06 and 2.20 Hz); 7.33 (m, 2H); 5.21 (br m, 1H); 4.68 (dt, 2H, J=13.9 and 6.59 Hz); 4.18 (q, 2H, J=6.96 Hz); 3.72 (d, 2H, J=1.47 Hz); 1.26 (t, 3H, J=7.14 Hz). Mass spectrum (electrospray) M+H=390.1

1. customTo a 0° C.
2. customfor 10 min
3. additionthe layers mixed
4. customseparated
5. extractionThe aqueous, layer was back extracted with 50 mL EtOAc
6. washthe combined organic layers washed with 150 mL water, and brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated