反应详情

温度

80 °C

A mixture of 1.1 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-(prop-2-ynyl)piperidine-3-carboxylate, 11 cm3 of triethylamine, 0.16 cm3 of tetrakis(triphenylphosphine)palladium, 0.053 g of cuprous iodide, and 0.47 cm3 of 1-bromo-2,5-difluorobenzene was stirred for 3 hours 15 minutes under an inert atmosphere at a temperature in the region of 80° C. After cooling to approximately 20° C., the reaction mixture had 30 cm3 of ethyl acetate and 30 cm3 of water added with stirring. The organic phase was separated, while the aqueous phase was extracted with 2 times 30 cm3 of ethyl acetate. The organic extracts were combined, washed with 3 times 25 cm3 of water, dried over sodium sulfate, and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. A product was obtained, which product was purified by chromatography under a nitrogen pressure of 50 kPa on a column of silica gel (particle size 20-45 μm; diameter 3.3 cm; 50 g), elution was carried out with ethyl acetate, and a fraction of 300 cm3 first was collected, followed by 32-cm3 fractions. Fractions 7 to 22 were combined and then concentrated under the above conditions. 0.91 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(2,5-difluorophenyl)prop-2-ynyl]piperidine-3-carboxylate was obtained in the form of a foam with an off-white color.

1. temperatureAfter cooling to approximately 20° C.
2. additionadded
3. stirringwith stirring
4. customThe organic phase was separated, while the aqueous phase
5. extractionwas extracted with 2 times 30 cm3 of ethyl acetate
6. washwashed with 3 times 25 cm3 of water
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
9. customA product was obtained
10. customwhich product was purified by chromatography under a nitrogen pressure of 50 kPa
11. washon a column of silica gel (particle size 20-45 μm; diameter 3.3 cm; 50 g), elution
12. customa fraction of 300 cm3 first was collected
13. concentrationconcentrated under the above conditions