Hydrochloric Acid → Methyl 2,2-dimethyl-6-oxo-6-phenylhexanoate

HRID 2299754Notes

Reaction equation

HRID 2299754 reaction equation
[Li+].CCC[CH2-].C(NC(C)C)(C)C.[C:13]([O:18][CH3:19])(=[O:17])[CH:14]([CH3:16])[CH3:15].I[CH2:21][CH2:22][CH2:23][C:24]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[O:28]CCO1.Cl>O1CCCC1.C(OCC)(=O)C.CCCCCC.CN(C)P(N(C)C)(N(C)C)=O>[CH3:15][C:14]([CH3:16])([CH2:21][CH2:22][CH2:23][C:24](=[O:28])[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[C:13]([O:18][CH3:19])=[O:17]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 11039Methyl isobutyrateHCID 61028n-Butyl lithiumHCID 137641302-(3-Iodopropyl)-2-phenyl-1,3-dioxolane

Product 1

HCID 11043092Methyl 2,2-dimethyl-6-oxo-6-phenylhexanoateYield 45%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 12679HexamethylphosphoramideSolventHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
-78 °C

Procedure

N-butyllithium (1.6N hexane solution, 2.16 ml) was added dropwise to a olution of diisopropylamine (0.529 ml) in tetrahydrofuran (5 ml) at −20° C. under nitrogen atmosphere. After stirring for 20 minutes, the mixture was cooled to −78° C., and methyl isobutyrate (0.397 ml) in tetrahydrofuran (5 ml) was added dropwise over 30 minutes. The reaction mixture was further stirred for 20 minutes, 2-(3-iodopropyl)-2-phenyl-1,3-dioxolane (1.00 g) and hexamethylphosphoramide (0.602 ml) were added. After stirring at −40° C. for 3 hours, dilute hydrochloric acid was added and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was dissolved in acetone (30 ml), 1N sulfuric acid (10 ml) was added and heated under reflux for 3 hours. The reaction mixture was cooled to room temperature, water was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The residue was subjected to silica gel chromatography to obtain methyl 2,2-dimethyl-6-oxo-6-phenylhexanoate (350 mg, yield 45%) as a colorless oil from an ethyl acetate-hexane (1:7, v/v)-eluted fraction.

Workup

  1. stirringThe reaction mixture was further stirred for 20 minutes
  2. stirringAfter stirring at −40° C. for 3 hours
  3. extractionextracted with ethyl acetate
  4. washThe ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in acetone (30 ml)
  8. addition1N sulfuric acid (10 ml) was added
  9. temperatureheated
  10. temperatureunder reflux for 3 hours
  11. temperatureThe reaction mixture was cooled to room temperature
  12. additionwater was added to the reaction mixture
  13. extractionextracted with ethyl acetate
  14. washThe ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride
  15. dry with materialdried (MgSO4)
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-eac7626d59534e74b18cb3bf713b66ad
Source dataset
uspto-grants-2002_12
Patent number
US06495581B1

Reaction notes

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