反应详情

Preparation of (trans)-benzyl 4-f2-chloroquinolin-8-yloxy)-3-fluoropiperidine-1-carboxylate: To a 0° C. solution of 4 mL 1:1 DMF:toluene was added neat POCl3 (0.360 ml, 3.94 mmol). The reaction mixture was warmed to ambient temperature, stirred 10 minutes, and then cooled to 0° C. A solution of 8-((trans)-1-(benzyloxycarbonyl)-3-fluoropiperidin-4-yloxy)quinoline 1-oxide (1.04 g, 2.62 mmol) in 1.2 mL 1:1 DMF:toluene was added dropwise by syringe to the reaction mixture, and the reaction mixture was heated in a 110° C. sand bath and stirred for 1 hours. The reaction mixture was cooled to ambient temperature and added dropwise to a stirring ice/saturated NaHCO3 mixture. The mixture was stirred 20 minutes, then extracted with DCM, and the combined extracts were dried (Na2SO4), filtered, and concentrated. The crude was purified on silica gel (Biotage 40S, loaded with 12:1hexanes:ethyl acetate, flushed 300 mL, then gradient to 5:1 hexanes:ethyl acetate) to give (trans)-benzyl 4-(2-chloroquinolin-8-yloxy)-3-fluoropiperidine-l-carboxylate (0.563 g, 1.36 mmol, 51.7% yield) as a syrup. MS APCI (+) m/z 415 (M+1) detected.

1. temperaturecooled to 0° C
2. temperaturethe reaction mixture was heated in a 110° C. sand bath
3. stirringstirred for 1 hours
4. temperatureThe reaction mixture was cooled to ambient temperature
5. stirringThe mixture was stirred 20 minutes
6. extractionextracted with DCM
7. dry with materialthe combined extracts were dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customThe crude was purified on silica gel (Biotage 40S
11. custom1hexanes:ethyl acetate, flushed 300 mL