反应详情

温度

75 °C

A mixture of 0.57 g of methyl (3R,4R)-4-[3-oxo-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate obtained as described in example 1, 0.462 g of 2-(2-bromoethylsulfanyl)-1,4-difluorobenzene, 0.253 g of potassium iodide and 1.05 g of potassium carbonate in 25 cm3 of acetonitrile is heated with stirring and under an inert atmosphere for 20 hours at a temperature in the region of 75° C. After cooling to a temperature in the region of 20° C., the reaction medium is filtered and the insoluble material is washed with 2 times 10 cm3 of acetonitrile. The filtrate is evaporated under reduced pressure (2 kPa) at a temperature in the region of 40° C. The evaporation residue is taken up with 50 cm3 of distilled water and 100 cm3 of ethyl acetate. The organic phase is washed with 3 times 30 cm3 of distilled water and 2 times 50 cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulfate and evaporated according to the conditions mentioned above. The oil obtained is purified by chromatography on a column of silica gel (particle size 70–200 μm; diameter 2.5 cm), eluting with a mixture of dichloromethane-methanol (9/10 by volume) and collecting fractions of 10 cm3. The fractions containing the expected product are pooled and then evaporated under reduced pressure (2 kPa) at a temperature in the region of 40° C. 0.4 g of methyl (3R,4R)-4-[3-oxo-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylsulfanyl)ethyl]-piperidine-3-carboxylate, in the form of an orange-colored viscous oil, is obtained.

1. customobtained
2. temperatureis heated
3. temperatureAfter cooling to a temperature in the region of 20° C.
4. filtrationthe reaction medium is filtered
5. washthe insoluble material is washed with 2 times 10 cm3 of acetonitrile
6. customThe filtrate is evaporated under reduced pressure (2 kPa) at a temperature in the region of 40° C
7. washThe organic phase is washed with 3 times 30 cm3 of distilled water and 2 times 50 cm3 of a saturated aqueous sodium chloride solution
8. dry with materialdried over magnesium sulfate
9. customevaporated
10. customThe oil obtained
11. customis purified by chromatography on a column of silica gel (particle size 70–200 μm; diameter 2.5 cm)
12. washeluting with a mixture of dichloromethane-methanol (9/10 by volume)
13. customcollecting fractions of 10 cm3
14. additionThe fractions containing the expected product
15. customevaporated under reduced pressure (2 kPa) at a temperature in the region of 40° C