反应详情

温度

20 °C

Phosphoryl chloride (76.9 cc) is added in the course of 30 minutes, with stirring and at between 10° and 15° C. to a mixture of trichloromethane (800 cc) and dimethylformamide (74.35 cc), and the mixture is stirred for 1 hour at a temperature in the region of 20° C. To the solution obtained, 6,7-difluoro-3,4-dihydrocarbostyril (65.8 g) is added in the course of 10 minutes at approximately 20° C. with vigorous stirring. The suspension obtained is heated to a temperature in the region of 60° C. and maintained at this temperature for 2 hours. The reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture is obtained. A mixture of ice (500 g) and water (500 cc) is added with vigorous stirring. The solid obtained is drained at approximately 5° C. and washed with water (3×300 cc) at 5° C. The wet product obtained and sodium acetate (60 g) are added simultaneously in the course of 1 hour to water (1.5 liters) at 90° C., so as to maintain the pH at approximately 6. The mixture is stirred for a further 30 minutes at 90° C., the temperature is allowed to fall to approximately 50° C. and the product is drained at this temperature and washed with water (3×300 cc) at approximately 20° C. 2-Chloro-6,7-difluoro-3-formyl-1,4-dihydroquinoline 70.18 g) is obtained in the form of a yellow solid, m.p. 260° C., which is used without further treatment for the subsequent steps.

1. customTo the solution obtained
2. customThe suspension obtained
3. temperatureis heated to a temperature in the region of 60° C.
4. temperaturemaintained at this temperature for 2 hours
5. concentrationThe reaction mixture is concentrated under reduced pressure (20 kPa) at 50° C. until a pasty mixture
6. customis obtained
7. additionis added with vigorous stirring
8. customThe solid obtained
9. customis drained at approximately 5° C.
10. washwashed with water (3×300 cc) at 5° C
11. customThe wet product obtained
12. temperatureso as to maintain the pH at approximately 6
13. stirringThe mixture is stirred for a further 30 minutes at 90° C.
14. customto fall to approximately 50° C.
15. washwashed with water (3×300 cc) at approximately 20° C