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

HRID 1986131Notes

Reaction equation

HRID 1986131 reaction equation
C[C:2]1([CH3:10])[O:9][C:7](=[O:8])[CH2:6][C:4](=[O:5])O1.N1C=CC=CC=1.[F:17][C:18]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:19]=1[CH2:20][O:21][C:22]1[CH:31]=[CH:30][C:25]([CH2:26]C(Cl)=O)=[CH:24][CH:23]=1.Cl>ClCCl>[F:17][C:18]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:19]=1[CH2:20][O:21][C:22]1[CH:23]=[CH:24][C:25]([CH2:26][C:4](=[O:5])[CH2:6][C:7]([O:9][CH2:2][CH3:10])=[O:8])=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 219645094-(2,6-Difluorobenzyloxy)benzylcarbonyl chloride

Product 1

HCID 21964507Ethyl 4-(4-(2,6-difluorobenzyloxy)phenyl)-3-oxobutyrate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

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.

Workup

  1. customresulted in an orange solution
  2. temperatureto warm to room temperature
  3. stirringstirred for an additional hour
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted twice with dichloromethane
  6. washThe combined organic layers were washed twice with 2M HCl and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to a solid
  10. temperaturerefluxed for 2.5 hours
  11. customThe solvent was removed in vacuo
  12. customto give a dark oil
  13. customThe residue was purified by flash chromatography on silica gel column (hex:ethyl acetate, 2:1)

Sources & evidence

ORD record
ord-250d996a17c649f69013332375ceb51b
Source dataset
uspto-grants-2009_06
Patent number
US07547802B2

Reaction notes

Loading…