反应详情

温度

0 °C

To a 0° C. solution of 8-((trans)-3-fluoropiperidin-4-yloxy)quinoline dihydrochloride (6.6 g, 26.8 mmol) and TEA (18.7 ml, 134.0 mmol) in 134 mL DCM was added benzyl carbonochloridate (4.4 ml, 29.5 mmol). The reaction mixture was stirred 15 minutes at 0° C., then warmed to ambient temperature and stirred another 16 hours. Water was added, and the mixture was extracted with DCM. The combined extracts were dried (Na2SO4), filtered, and concentrated. The crude was purified on silica gel (Biotage 40M, loaded with 4:1hexanes:ethyl acetate and 500 mL flushed, then gradient to 1:1 hexanes:ethyl acetate) to give (trans)-benzyl 3-fluoro-4-(quinolin-8-yloxy)piperidine-1-carboxylate (5.2 g, 13.67 mmol, 51.01% yield) as an oil. MS APCI (+) m/z 381 (M+1) detected.

1. temperaturewarmed to ambient temperature
2. stirringstirred another 16 hours
3. extractionthe mixture was extracted with DCM
4. dry with materialThe combined extracts were dried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated
7. customThe crude was purified on silica gel (Biotage 40M
8. custom1hexanes:ethyl acetate and 500 mL flushed