반응 #9972

반응 방정식

sodium hydrogencarbonate

butyl lithium hexane

3-Bromo-5-(4-fluorophenyl)-4-(pyridin-4-yl)pyrazole

1,2,3,5,6,7,8,8a-octahydroindolizin-7-one

→

title compound

수율 22.0%

(±)-5-(4-Fluorophenyl)-3-(7-hydroxy-1,2,3,5,6,7,8,8a-octahydroindolizin-7-yl)-4-(pyridin-4-yl)pyrazole

수율 22.0%

용매

tetrahydrofuran

반응 조건

후처리

1. 1
   workup.STIRRINGthe resulting mixture was stirred first at −78° C. for 2 hours
2. 2
   workup.WAITat room temperature for 1 hour
3. 3
   추출extracted with ethyl acetate
4. 4
   세척The organic layer was washed with water
5. 5
   건조dried over anhydrous sodium sulfate
6. 6
   기타the solvent was removed by distillation under reduced pressure
7. 7
   기타The residue was purified by column chromatography through silica gel (eluent, ethyl acetate:methanol:isopropylamine=20:1:1)

실험 절차

3-Bromo-5-(4-fluorophenyl)-4-(pyridin-4-yl)pyrazole (3.18 g (10 mmol), prepared as described in 1)) was dissolved in tetrahydrofuran (32 ml). To the solution was added a solution of 1.6 M butyl lithium/hexane (13.75 ml, 13.75 mmol) at −78° C., and the resulting mixture was stirred for 10 minutes. To the mixture was added 1,2,3,5,6,7,8,8a-octahydroindolizin-7-one (1.53 g, 11 mmol) at −78° C., and the resulting mixture was stirred first at −78° C. for 2 hours, then at room temperature for 1 hour. At the end of this time, the reaction mixture was added to a saturated aqueous solution of sodium hydrogencarbonate and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate and the solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography through silica gel (eluent, ethyl acetate:methanol:isopropylamine=20:1:1), to give the title compound (830 mg) as a pale yellow powder (yield 22%).

출처