反应详情

A solution of 1 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(2,3,5-trifluorophenyl)prop-2-ynyl]piperidine-3-carboxylate in 10 cm3 of a 5N aqueous hydrochloric acid solution is stirred for 4 hours at a temperature in the region of 80° C. After cooling to a temperature in the region of 20° C., 10 cm3 of water, then 10 cm3 of chloroform, and then 1.9 g of powdered sodium hydrogen carbonate are added. The mixture is extracted with 3 times 10 cm3 of chloroform. The organic phases are pooled, dried over sodium sulfate, filtered, and then concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained is purified by chromatography under a nitrogen pressure of 50 kPa, on a column of silica gel (particle size 20–45μ; diameter 2.5 cm; 30 g), eluting with a mixture of dichloromethane-methanol (96/4 by volume) and collecting first a fraction of 150 cm3, and then fractions of 10 cm3. Fractions 5 to 22 are pooled, and then concentrated as above. 0.583 g of (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(2,3,5-trifluorophenyl)prop-2-ynyl]piperidine-3-carboxylic acid, in the form of a green-colored solid which melts at around 70° C., is obtained.

1. extractionThe mixture is extracted with 3 times 10 cm3 of chloroform
2. dry with materialdried over sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
5. customThe residue obtained
6. customis purified by chromatography under a nitrogen pressure of 50 kPa
7. washon a column of silica gel (particle size 20–45μ; diameter 2.5 cm; 30 g), eluting with a mixture of dichloromethane-methanol (96/4 by volume)
8. customcollecting first a fraction of 150 cm3
9. concentrationconcentrated as above