反应详情

A solution of potassium permanganate (115 g) in water (1.215 liters) is added in the course of 1 hour to a stirred suspension, cooled to 10° C., of 2-chloro-6,7-difluoro-3-formyl-1,4-dihydro quinoline (70.18 g) in N aqueous potassium hydroxide solution (970 cc) while the temperature is maintained at between 10° and 14° C. The temperature is allowed to rise to approximately 20° C. and the mixture is stirred for a further 30 minutes at this temperature. Sodium dithionite (38.5 g) is added and the mixture is stirred for 10 minutes at a temperature in the region of 20° C., filtered through diatomaceous silica and washed with water (3×200 cc). The filtrate and the aqueous washing phases are combined and treated with 35% strength aqueous hydrochloric acid solution (140 cc). The precipitate formed is extracted with ethyl acetate (4×800 cc). The combined organic extracts are washed with water (2×500 cc), dried over magnesium sulphate, filtered and concentrated under reduced pressure (20 kPa) at 50° C. The residue is taken up with ethyl ether (400 cc), drained and washed with the same solvent (2×200 cc). 2-Chloro-6,7-difluoro-3-quinolinecarboxylic acid (49.2 g) is obtained in the form of a beige solid, m.p. 232° C., which is used without further purification for the subsequent steps.

1. temperatureis maintained at between 10° and 14° C
2. customto rise to approximately 20° C.
3. stirringthe mixture is stirred for 10 minutes at a temperature in the region of 20° C.
4. filtrationfiltered through diatomaceous silica
5. washwashed with water (3×200 cc)
6. additiontreated with 35% strength aqueous hydrochloric acid solution (140 cc)
7. customThe precipitate formed
8. extractionis extracted with ethyl acetate (4×800 cc)
9. washThe combined organic extracts are washed with water (2×500 cc)
10. dry with materialdried over magnesium sulphate
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure (20 kPa) at 50° C
13. washwashed with the same solvent (2×200 cc)