反应详情

温度

14 °C

3-Bromomethyl-7-(2,6-difluorobenzyl)-4,7-dihydro-5-isobutyryl-4-oxo-2-phenylthieno[2,3-b]pyridine (40 g) was dissolved in methanesulfonic acid (200 ml) with cooling at 13 to 15° C. and then treated dropwise with a solution of sodium nitrate (6.59 g) in methanesulfonic acid (100 ml) over a period of 1 hour. The mixture was stirred as it was for 2.5 hours, and then poured into a cool water (2800 ml), and the crystal precipitated was recovered by a filtration, washed with water until the pH of the wash became 5 to 6, and then dried in vacuo at 50° C. for 24 hours. The rude crystal thus obtained was suspended in ethyl acetate (300 ml), and the reaction mixture was stirred at 50° C. for 1 hour and then with cooling on ice for 1 hour, and the crystal was recovered by a filtration, washed with a cooled ethyl acetate (100 ml), dried in vacuo at 40° C. for 5 hours to obtain the title compound (32.4 g, 74.5%).

1. customthe crystal precipitated
2. filtrationwas recovered by a filtration
3. washwashed with water until the pH of the wash
4. customdried in vacuo at 50° C. for 24 hours
5. customThe rude crystal thus obtained
6. stirringthe reaction mixture was stirred at 50° C. for 1 hour
7. temperaturewith cooling on ice for 1 hour
8. filtrationthe crystal was recovered by a filtration
9. washwashed with a cooled ethyl acetate (100 ml)
10. customdried in vacuo at 40° C. for 5 hours