反应详情

温度

20 °C

A mixture of 1.07 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-(prop-2-ynyl)piperidine-3-carboxylate in 10 cm3 of triethylamine was stirred for 5 minutes under an inert atmosphere at a temperature in the region of 20° C. 0.156 g of tetrakis(triphenylphosphine)palladium, 0.051 gof cuprous iodide, and 0.78 g of 1-bromo-2,6-difluorobenzene were added. The mixture was stirred for 3 hours 30 minutes 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. After stirring for 10 minutes, the mixture was separated by settling. After separating off the organic phase, the aqueous layer was extracted with 2 times 30 cm3 of ethyl acetate. The organic extracts were combined, washed with 3 times 30 cm3 of water, dried over sodium sulfate, filtered, and concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was purified by chromatography under a nitrogen pressure of 50 kPa on a column of silica gel (particle size 20-45 μm; diameter 3 cm; 50 g), elution was carried out with pure ethyl acetate, and first a fraction of 300 cm3 were collected, followed by 38-cm3 fractions. Fractions 6 to 16 were combined and concentrated as above. 0.55 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(2,6-difluorophenyl)prop-2-ynyl]piperidine-3-carboxylate was obtained in the form of a foam with a pale yellow color.

1. stirringThe mixture was stirred for 3 hours 30 minutes at a temperature in the region of 80° C
2. temperatureAfter cooling to approximately 20° C.
3. additionadded
4. stirringAfter stirring for 10 minutes
5. customthe mixture was separated
6. customAfter separating off the organic phase
7. extractionthe aqueous layer was extracted with 2 times 30 cm3 of ethyl acetate
8. washwashed with 3 times 30 cm3 of water
9. dry with materialdried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
12. customThe residue obtained
13. customwas purified by chromatography under a nitrogen pressure of 50 kPa
14. washon a column of silica gel (particle size 20-45 μm; diameter 3 cm; 50 g), elution
15. customfirst a fraction of 300 cm3 were collected
16. concentrationconcentrated as above