反应详情

温度

-2 °C

0.261 g of sodium borohydride was added, in several portions, to a mixture of 0.4 g of methyl (3RS,4RS)-4-[3-hydroxyimino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-3-acetate in 25-cm3 of methanol cooled in the region of −2° C., with stirring and under an inert atmosphere. The reaction mixture was stirred in the region of 0° C. for 20 minutes and then 0.14 g of molybdenum trioxide wereadded. The reaction mixture was stirred in the region of 20° C. for 24 hours and then it was cooled in the vicinity of −2° C. and 0.261 g of sodium borohydride and 0.14 g of molybdenum trioxide were again added. The reaction mixture was stirred for 18 hours in the region of 20° C. and then filtered on celite. The filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The evaporation residue was purified by chromatography under an argon pressure of 50 kPa, on a column of silica gel (particle size 40-60 μm; diameter 3 cm), eluting with a successive mixture of cyclohexane-ethyl acetate (50/50 by volume) and then dichloromethane-methanol (90/10 by volume) and collecting 10-cm3 fractions. Fractions 26 to 41 were combined and then concentrated to dryness according to the conditions described above. 0.202 g of methyl (3RS,4RS)-4-[3-(R,S)-amino-3-(3-fluoro-6-methoxyquinolin-4-yl)propyl]-1-[2-(2,5-difluorophenylthio)ethyl]piperidine-3-acetate were obtained in the form of a colorless oil.

1. stirringThe reaction mixture was stirred in the region of 0° C. for 20 minutes
2. stirringThe reaction mixture was stirred in the region of 20° C. for 24 hours
3. additionwere again added
4. stirringThe reaction mixture was stirred for 18 hours in the region of 20° C.
5. filtrationfiltered on celite
6. concentrationThe filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C
7. customThe evaporation residue was purified by chromatography under an argon pressure of 50 kPa
8. washon a column of silica gel (particle size 40-60 μm; diameter 3 cm), eluting with a successive mixture of cyclohexane-ethyl acetate (50/50 by volume)
9. customdichloromethane-methanol (90/10 by volume) and collecting 10-cm3 fractions
10. concentrationconcentrated to dryness