反应详情

温度

60 °C

A suspension of 2-chloro-6,7-difluoroquinoline-3-carboxylic acid (14.13 g) in thionyl chloride (29 cc) and trichloromethane (220 cc) is heated to a temperature in the region of 60° C. for 4 hours. The solution obtained is concentrated to dryness under reduced pressure (20 kPa) at approximately 60° C. The residue obtained is taken up with n-hexene (75 cc), drained and washed with the same solvent (2×60 cc). The yellow solid obtained (14.4 g) is dissolved in tetrahydrofuran (115 cc). This solution is introduced dropwise, with stirring, in the course of 35 minutes at between 5° and 10° C. into a solution (70 cc) of magnesium chelate of ethyl monomalonate in tetrahydrofuran, prepared under the conditions described below. The temperature is allowed to rise to approximately 20 C. and the mixture is stirred for a further 2 hours under these conditions. The solution obtained is introduced dropwise, with stirring, in the course of 30 minutes and at a temperature in the region of 5° C. into 0.5 N sulphuric acid (560 cc). The temperature of the suspension obtained is allowed to rise to 20° C. and the mixture is stirred for a further 1 hour and a half at this temperature. The product is extracted with ethyl acetate (3×250 cc). The combined organic extracts are washed with water (2×250 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (20 kPa) at 50° C. The residue obtained is taken up with n-hexane (50 cc) containing isopropyl ether (20%), drained, washed with the same mixture (10 cc) and recrystallized in isopropanol (60 cc) containing n-hexane (30%). Ethyl 3-(2-chloro-6,7-difluoro-3-quinolyl)-3-oxo-propionate (11.84 g) is obtained in the form of a cream-colored solid, m.p. 107° C.

1. customThe solution obtained
2. concentrationis concentrated to dryness under reduced pressure (20 kPa) at approximately 60° C
3. customThe residue obtained
4. washwashed with the same solvent (2×60 cc)
5. customThe yellow solid obtained (14.4 g)
6. additionThis solution is introduced dropwise
7. customprepared under the conditions
8. customThe solution obtained
9. additionis introduced dropwise
10. customThe temperature of the suspension obtained
11. customto rise to 20° C.
12. stirringthe mixture is stirred for a further 1 hour
13. extractionThe product is extracted with ethyl acetate (3×250 cc)
14. washThe combined organic extracts are washed with water (2×250 cc)
15. dry with materialdried over magnesium sulphate
16. filtrationfiltered
17. concentrationconcentrated to dryness under reduced pressure (20 kPa) at 50° C
18. customThe residue obtained
19. washwashed with the same mixture (10 cc)
20. customrecrystallized in isopropanol (60 cc)
21. additioncontaining n-hexane (30%)