Lithium Hydroxide → Methyl 6-(4-chlorophenyl)-2,2-dimethyl-4-oxohexanoate

HRID 327247Notes

Reaction equation

HRID 327247 reaction equation
[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([Cl:9])=[CH:5][CH:4]=1)[CH3:2].[C:10]([O-])(=O)CC.C[Si](C)(C)N[Si](C)(C)C.[K].[CH3:25][C:26]1([CH3:33])[CH2:31][C:30](=[O:32])[O:29][C:27]1=[O:28].[Li+].[OH-]>C1COCC1.C1(C)C=CC=CC=1.CO.O>[Cl:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:1][CH2:2][C:30](=[O:32])[CH2:31][C:26]([CH3:33])([CH3:25])[C:27]([O:29][CH3:10])=[O:28])=[CH:4][CH:5]=1

Participants

9

Reactant 4

HCID 3939Lithium HydroxideHCID 870672,2-Dimethylsuccinic anhydrideHCID 45051783Silanamine, 1,1,1-trimethyl-N-(trimethylsilyl)-, potassium saltHCID 86747418Ethyl (4-chlorobenzene) propanoate

Product 1

HCID 18947527Methyl 6-(4-chlorophenyl)-2,2-dimethyl-4-oxohexanoate

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-60 °C

Procedure

To a solution of ethyl (4-chlorobenzene)-propanoate (Step B, 10 g) in dry THF (500 mL) at -78° C. was added 0.58M potassium hexamethyldisilazane in toluene (243 mL). The mixture was stirred at -60° C. for one hour. Then a solution of 2,2-dimethylsuccinic anhydride (6 g) in THF (100 mL) was added slowly and the mixture was slowly warmed to room temperature and finally stirred for 18 hours. Water (1000 mL) was added and the organic layer separated, The aqueous layer was washed with EtOAc (3×250 ml) and acidified with 1N HCl. The aqueous layer was extracted with EtOAc, the extract was dried (Na2SO4) and evaporated to give a residue which was dissolved in THF (100 mL) and MeOH (200 mL) and treated at reflux with 1N LiOH (100 mL) for 4 hours. The mixture was cooled to room temperature and concentrated under vacuum until H2O distilled off. Water (500 mL) was added, the mixture acidified with 1N aq. HCl, extracted with EtOAc, the extract was dried (Na2SO4) and evaporated to give the title product as its carboxylic acid. The compound was treated with diazomethane in ether, evaporated to dryness and chromatographed over silica gel, eluting with EtOAc-hexane (10:90) to give the title product as a white solid; m.p. 52°-54° C.

Workup

  1. temperaturethe mixture was slowly warmed to room temperature
  2. stirringfinally stirred for 18 hours
  3. customthe organic layer separated
  4. washThe aqueous layer was washed with EtOAc (3×250 ml)
  5. extractionThe aqueous layer was extracted with EtOAc
  6. dry with materialthe extract was dried (Na2SO4)
  7. customevaporated
  8. customto give a residue which
  9. temperatureThe mixture was cooled to room temperature
  10. concentrationconcentrated under vacuum until H2O
  11. distillationdistilled off
  12. additionWater (500 mL) was added
  13. extractionextracted with EtOAc
  14. dry with materialthe extract was dried (Na2SO4)
  15. customevaporated

Sources & evidence

ORD record
ord-479928ad35be45998931a76ce24d0d00
Source dataset
uspto-grants-1993_12
Patent number
US05272145

Reaction notes

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