反应详情

温度

0 °C

Through a 0° C. solution of 0.6 g (1.6 mmol) ethyl(2-{(tert-butoxycarbonyl)[2,2-difluoro-2-(2-pyridinyl)ethyl]amino}-5-chloro-3-fluoro4-pyridinyl)acetate 1-4 in 12 mL EtOAc was passed a steady stream of HCl gas for 20 min, then the reaction mixture was allowed to stir at 0° C. for 20 min. A precipitate formed so 1 mL MeOH was added to make the reaction homogeneous and HCl gas was passed through the mixture for another 15 min., then a stream of N2 gas for 5 min, then the mixture poured into 300 mL EtOAc/100 mL 2M NaOH/15 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-(2-pyridinyl)ethyl]amino}-3-fluoro-4-pyridinyl)acetate 1-5 which was used without further purification. 1H NMR (400 mHz, CDCl3) δ8.66 (br d, 1H, J=4.76 Hz); 7.88 (s, 1H); 7.82 (ddd, 1H, J=7.7, 7.7, and 1.64 Hz); 7.69 (d, 1H, J=7.87 Hz); 7.39 (dd, 1H, J=4.76 and 7.33 Hz); 5.21 (br m, 1H); 4.43 (dt, 2H, J=13.9 and 6.05 Hz); 4.18 (q, 2H, J=7.14 Hz); 3.75 (d, 2H, J=1.65 Hz); 1.26 (t, 3H, J=7.14 Hz). Mass spectrum (electrospray) M+H=374.1

1. customThrough a 0° C.
2. customfor 20 min
3. additionwas added
4. waitwas passed through the mixture for another 15 min.
5. additionthe layers mixed
6. customseparated
7. extractionThe aqueous, layer was back extracted with 50 mL EtOAc
8. washthe combined organic layers washed with 150 mL water, and brine
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated