반응 #53293

반응 방정식

HCl

4-(2,6-Difluorobenzyloxy)benzylcarbonyl chloride

Meldrum's acid

pyridine

→

title compound

Ethyl 4-(4-(2,6-difluorobenzyloxy)phenyl)-3-oxobutyrate

용매

dichloromethane

dichloromethane

dichloromethane

반응 조건

후처리

1. 1
   기타resulted in an orange solution
2. 2
   온도to warm to room temperature
3. 3
   workup.STIRRINGstirred for an additional hour
4. 4
   기타The phases were separated
5. 5
   추출the aqueous phase was extracted twice with dichloromethane
6. 6
   세척The combined organic layers were washed twice with 2M HCl and brine
7. 7
   건조dried over Na2SO4
8. 8
   여과filtered
9. 9
   농축concentrated to a solid
10. 10
    온도refluxed for 2.5 hours
11. 11
    기타The solvent was removed in vacuo
12. 12
    기타to give a dark oil
13. 13
    기타The residue was purified by flash chromatography on silica gel column (hex:ethyl acetate, 2:1)

실험 절차

To a solution of Meldrum's acid (0.846 g, 5.8 mmol) in dichloromethane (5 ml) was added pyridine (2 ml) over a period of 10 minutes at 0° C. To this solution was added 4-(2,6-Difluorobenzyloxy)benzylcarbonyl chloride (Step D, 1.71 g, 5.7 mmol) in dichloromethane (5 ml), which resulted in an orange solution. The dark orange solution was stirred for 1 hour at 0° C., allowed to warm to room temperature and stirred for an additional hour. The reaction mixture was diluted with dichloromethane and poured onto 2M HCl and ice. The phases were separated and the aqueous phase was extracted twice with dichloromethane. The combined organic layers were washed twice with 2M HCl and brine, dried over Na2SO4, filtered and concentrated to a solid. The solid was suspended in abs EtOH (15 ml) and refluxed for 2.5 hours. The solvent was removed in vacuo to give a dark oil. The residue was purified by flash chromatography on silica gel column (hex:ethyl acetate, 2:1) to provide the title compound as a white solid.

출처