Reaction #53293

Reaction equation

HCl

4-(2,6-Difluorobenzyloxy)benzylcarbonyl chloride

Meldrum's acid

pyridine

→

title compound

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

Solvents

dichloromethane

dichloromethane

dichloromethane

Conditions

Workup

1. 1
   Otherresulted in an orange solution
2. 2
   Temperatureto warm to room temperature
3. 3
   workup.STIRRINGstirred for an additional hour
4. 4
   OtherThe phases were separated
5. 5
   Extractionthe aqueous phase was extracted twice with dichloromethane
6. 6
   WashThe combined organic layers were washed twice with 2M HCl and brine
7. 7
   Dryingdried over Na2SO4
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated to a solid
10. 10
    Temperaturerefluxed for 2.5 hours
11. 11
    OtherThe solvent was removed in vacuo
12. 12
    Otherto give a dark oil
13. 13
    OtherThe residue was purified by flash chromatography on silica gel column (hex:ethyl acetate, 2:1)

Procedure

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.

Source