反应详情

A suspension of 38.75 g of 2,7-dichloro-6-fluoro-quinoline-3-carboxylic acid in 410 cm3 of trichloromethane and 24 cm3 of thionyl chloride is heated at a temperature close to 60° C., with stirring, for 6 hours. The solution obtained is concentrated to dryness under reduced pressure (20 kPa) at 50° C. The dry extract is twice taken up in a total of 200 cm3 of toluene and again concentrated under reduced pressure under the same conditions as above. The yellow solid obtained, which melts at 124° C., is dissolved in 230 cm3 of anhydrous tetrahydrofuran. The solution obtained is introduced dropwise, with stirring, in the course of 30 minutes, at between 5° and 10° C., into 200 cm3 of a solution of magnesium chelate in tetrahydrofuran, the preparation of which is described below. The temperature is allowed to rise to 20° C. and the mixture is stirred for 1 hour and a half at this temperature. The solution obtained is introduced dropwise, with vigorous stirring, at a temperature close to 5° C., into 1 liter of 0.5 N sulphuric acid. The temperature of the suspension obtained is allowed to rise to 20° C. and the suspension is stirred for a further 2 hours at this temperature. The suspension is extracted with 1 liter of ethyl acetate and the organic and aqueous phases are filtered through diatomaceous silica for filtration, which enables a small amount of insoluble matter to be removed, and the aqueous phase is extracted twice more with 500 cm3 of ethyl acetate. The combined organic extracts are washed with twice 500 cm3 of water, dried over magnesium sulphate and filtered and the filtrate is concentrated to dryness under reduced pressure (20 kPa) at 40° C. The residue is taken up in 100 cm3 of diisopropyl ether at 20° C., drained and washed with twice 30 cm3 of diisopropyl ether. 40.55 g of ethyl 3-(2,7-dichloro-6-fluoro-3-quinolyl)-3-oxopropionate are obtained in the form of a beige solid melting at 112°-114° C. This product is used for the subsequent steps without further purification.

1. temperatureis heated at a temperature
2. customclose to 60° C.
3. customThe solution obtained
4. concentrationis concentrated to dryness under reduced pressure (20 kPa) at 50° C
5. extractionThe dry extract
6. concentrationagain concentrated under reduced pressure under the same conditions as above
7. customThe yellow solid obtained
8. customThe solution obtained
9. additionis introduced dropwise
10. customthe preparation of which
11. customto rise to 20° C.
12. stirringthe mixture is stirred for 1 hour
13. customThe solution obtained
14. additionis introduced dropwise, with vigorous stirring, at a temperature
15. customThe temperature of the suspension obtained
16. customto rise to 20° C.
17. stirringthe suspension is stirred for a further 2 hours at this temperature
18. extractionThe suspension is extracted with 1 liter of ethyl acetate
19. filtrationthe organic and aqueous phases are filtered through diatomaceous silica for filtration, which
20. customto be removed
21. extractionthe aqueous phase is extracted twice more with 500 cm3 of ethyl acetate
22. washThe combined organic extracts are washed with twice 500 cm3 of water
23. dry with materialdried over magnesium sulphate
24. filtrationfiltered
25. concentrationthe filtrate is concentrated to dryness under reduced pressure (20 kPa) at 40° C
26. customis taken up in 100 cm3 of diisopropyl ether at 20° C.
27. washwashed with twice 30 cm3 of diisopropyl ether