反应详情

A solution of the mixture of 4-(2,5-difluorobenzoyl)nicotinic acid and 3-(2,5-difluorobenzoyl)isonicotinic acid of Preparative Example 3 (61.07 g) in 20% oleum (100 mL) is heated at 140° C. while 20% oleum is added in four portions (13.2 mL each) at 20 min-intervals. After the fourth addition the mixture is heated for 20 min, then it is cooled to room temperature and quenched with a mixture of ice (1,500 g), water (1,500 mL) and 35% NaOH (350 mL). The mixture is extracted four times with methylene chloride (1×1,000 mL followed by 3×500 mL). The combined organic solutions are washed with water (2×1,000 mL), dried (Na2SO4) and the solvent removed by roto-evaporation. The dark-red solid obtained (56.0 g) is dissolved in boiling THF (840 mL) and decolorizing charcoal (8.40 g) is added. After 30 min the mixture is filtered while hot and the filtrate concentrated to 200 mL. The precipitate obtained is collected by suction filtration to give 6,9-difluorobenzo[g]isoquinoline-5,10-dione (43.00 g).

1. additionis added in four portions (13.2 mL each) at 20 min-intervals
2. additionAfter the fourth addition the mixture
3. temperatureis heated for 20 min
4. customquenched with a mixture of ice (1,500 g), water (1,500 mL) and 35% NaOH (350 mL)
5. extractionThe mixture is extracted four times with methylene chloride (1×1,000 mL followed by 3×500 mL)
6. washThe combined organic solutions are washed with water (2×1,000 mL)
7. dry with materialdried (Na2SO4)
8. customthe solvent removed by roto-evaporation
9. customThe dark-red solid obtained (56.0 g)
10. dissolutionis dissolved
11. additionis added
12. filtrationAfter 30 min the mixture is filtered while hot and the filtrate
13. concentrationconcentrated to 200 mL
14. customThe precipitate obtained
15. filtrationis collected by suction filtration