Hydrochloric Acid → 3-(3,4-Dichloro-phenyl)-dihydro-furan-2-one

HRID 357243Notes

Reaction equation

HRID 357243 reaction equation
[CH3:1][O:2][C:3](=[O:13])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([Cl:11])=[C:7]([Cl:12])[CH:6]=1.Br[CH2:15]CO.Cl>C1COCC1>[Cl:12][C:7]1[CH:6]=[C:5]([CH:4]2[CH2:15][CH2:1][O:2][C:3]2=[O:13])[CH:10]=[CH:9][C:8]=1[Cl:11]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 108982-BromoethanolHCID 1268257Methyl 2-(3,4-dichlorophenyl)acetate

Product 1

HCID 118064963-(3,4-Dichloro-phenyl)-dihydro-furan-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
45 °C

Procedure

Heat [(CH3)3Si]2NLi (230 ml, 1.0M in THF) under N2 to 45° C. and add 3,4 dichlorophenyl acetic acid methyl ester (40 g, 0.183 moles) dissolved in 60 ml of dry THF dropwise over 2 h. Stir the solution at 45° C. for another 2.5 h. Cool the solution to room temperature, add a dry THF solution (30 ml.) of THP-protected Br(CH2)2OH dropwise over 1 h., and stir the solution for 24 h. Cool the solution in an ice bath and quench the reaction by adding, dropwise, 250 ml. of 1.0M aqueous HCl. Extract the solution with Et2 O, wash the organic layer twice with 1.0M aqueous HCl, then with water, and dry over anhydrous Na2SO4. Remove the solvent, dissolve the residue in CH3OH and add 0.5 g of pTSA. Stir the solution at room temperature overnight, remove the solvent, add CH3OH (500 ml) and stir for 6 h. Remove the solvent again, add more CH3OH (500 ml.), stir overnight and remove the solvent. Dissolve the resulting oil in CH2Cl2 (1200 ml.), wash twice with saturated aqueous NaHCO3, then water, and dry over anhydrous Na2SO4. Remove the solvent in vacuo. Purify the reaction mixture by flash chromatography (SiO2) using EtOAc: hexanes (3:7) as eluent. Yield: 22 g. Cl-MS: 231 (100%), 233 (65%).

Workup

  1. temperatureCool the solution to room temperature
  2. stirringstir the solution for 24 h
  3. temperatureCool the solution in an ice bath
  4. customquench
  5. customthe reaction
  6. additionby adding
  7. extractionExtract the solution with Et2 O
  8. washwash the organic layer twice with 1.0M aqueous HCl
  9. dry with materialwith water, and dry over anhydrous Na2SO4
  10. customRemove the solvent
  11. dissolutiondissolve the residue in CH3OH
  12. additionadd 0.5 g of pTSA
  13. stirringStir the solution at room temperature overnight
  14. customremove the solvent
  15. additionadd CH3OH (500 ml)
  16. stirringstir for 6 h
  17. customRemove the solvent again
  18. additionadd more CH3OH (500 ml.)
  19. stirringstir overnight
  20. customremove the solvent
  21. dissolutionDissolve the resulting oil in CH2Cl2 (1200 ml.)
  22. washwash twice with saturated aqueous NaHCO3
  23. dry with materialwater, and dry over anhydrous Na2SO4
  24. customRemove the solvent in vacuo
  25. customPurify the reaction mixture by flash chromatography (SiO2)

Sources & evidence

ORD record
ord-cc5388282a324eeaa4b2929d691ae157
Source dataset
uspto-grants-1998_11
Patent number
US05840725

Reaction notes

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