反应详情

To a solution of 0.58 g (1.49 mmol) ethyl(5-chloro-2-{[2,2-difluoro-2-(1-oxido-2-pyridinyl)ethyl]amino}-3-fluoro-4-pyridinyl)acetate 1-8 in 10 mL MeOH was added 1.64 mL (1.64 mmol, 1M aqueous solution) LiOH and the reaction mixture allowed to stir 16 hours at room temperature, then 0.16 mL (0.16 mmol) more LiOH was added and the mixture heated to 45° C. for 4 h, then cooled. To this was added 0.15 mL (1.79 mmol, 12M solution) HCl and the mixture concentrated to give (5-chloro-2-{[2,2-difluoro-2-(1-oxido-2-pyridinyl)ethyl]amino}-3-fluoro-4-pyridinyl)acetic acid 1-9 (mixed with LiCl). 1H NMR (400 mHz, CD3OD) δ8.36 (br d, 1H, J=6.23 Hz); 7.66 (dd, 1H, J=7.87 and 2.19 Hz); 7.56 (s, 1H); 7.51 (m, 2H,); 4.58 (t, 2H, J=13 Hz); 3.63 (d, 2H, J=1.65 Hz);

1. temperaturethe mixture heated to 45° C. for 4 h
2. temperaturecooled
3. concentrationthe mixture concentrated