Hydrochloric Acid → Ethyl 2-acetyl-5,5-dimethyl-4-oxohexanoate

HRID 1514637Notes

Reaction equation

HRID 1514637 reaction equation
[O:1]=[C:2]([CH3:9])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].Br[CH2:11][C:12](=[O:17])[C:13]([CH3:16])([CH3:15])[CH3:14].Cl>O1CCCC1>[C:2]([CH:3]([CH2:11][C:12](=[O:17])[C:13]([CH3:16])([CH3:15])[CH3:14])[C:4]([O:6][CH2:7][CH3:8])=[O:5])(=[O:1])[CH3:9]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8868Ethyl AcetoacetateHCID 21642Bromopinacolone

Product 1

HCID 11775940Ethyl 2-acetyl-5,5-dimethyl-4-oxohexanoateYield 93.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A 6.214 g portion of sodium hydride (55% dispersion in oil) was washed with hexane, 150 ml of tetrahydrofuran was added thereto and, under ice-cooling, a solution prepared by dissolving 18.534 g of ethyl 3-oxobutanoate in 75 ml of tetrahydrofuran was added dropwise thereto. After stirring at room temperature for 30 minutes, this solution was added dropwise, under ice-cooling, to a solution prepared by dissolving 25.500 g of 1-bromo-3,3-dimethyl-2-butanone in 150 ml of tetrahydrofuran, followed by stirring overnight at room temperature. After adding 171 ml of 1 M hydrochloric acid to the reaction liquid, tetrahydrofuran was evaporated under a reduced pressure. The residue was extracted with diethyl ether, and the organic layer was washed with water (twice) and saturated brine and then dried over anhydrous sodium sulfate. By evaporating the solvent under a reduced pressure, 30.51 g of ethyl 2-acetyl-5,5-dimethyl-4-oxohexanoate was obtained as yellow oil. A 15.00 g portion of this product was dissolved in 250 ml of acetic acid, and 9.48 ml of 4-fluorophenethylamine was added thereto, followed by stirring at 100° C. for 4 hours. The solvent was evaporated under a reduced pressure. The residue was dissolved in ethyl acetate and washed with water, a 1 M sodium hydroxide aqueous solution (twice) and saturated brine. After drying with anhydrous sodium sulfate, the solvent was evaporated under a reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:15-1:10) to obtain 15.91 g of ethyl 5-tert-butyl-1-[2-(4-fluorophenyl)ethyl]-2-methyl-1H-pyrrole-3-carboxylate as a colorless solid.

Workup

  1. washA 6.214 g portion of sodium hydride (55% dispersion in oil) was washed with hexane, 150 ml of tetrahydrofuran
  2. additionwas added
  3. temperatureunder ice-cooling
  4. customa solution prepared
  5. additionwas added dropwise
  6. additionthis solution was added dropwise, under ice-
  7. temperaturecooling, to a solution
  8. customprepared
  9. stirringby stirring overnight at room temperature
  10. customwas evaporated under a reduced pressure
  11. extractionThe residue was extracted with diethyl ether
  12. washthe organic layer was washed with water (twice) and saturated brine
  13. dry with materialdried over anhydrous sodium sulfate
  14. customBy evaporating the solvent under a reduced pressure

Sources & evidence

ORD record
ord-02dfff7cf804415089cc6350073be1a7
Source dataset
uspto-grants-2012_07
Patent number
US08222274B2

Reaction notes

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