Isobutyric Acid → 2,2-Dimethyl-4-phenylbutanoic acid

HRID 530498Notes

Reaction equation

HRID 530498 reaction equation
C(NC(C)C)(C)C.[H-].[Na+].[C:10]([OH:15])(=[O:14])[CH:11]([CH3:13])[CH3:12].C([Li])CCC.CCCCCC.Br[CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>C1COCC1>[CH3:12][C:11]([CH3:13])([CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:10]([OH:15])=[O:14]

Participants

8

Reactant 6

HCID 6590Isobutyric AcidHCID 7666Phenethyl bromideHCID 7912DiisopropylamineHCID 8058HexaneHCID 24758Sodium hydrideHCID 178418339Butyllithium

Product 1

HCID 124737192,2-Dimethyl-4-phenylbutanoic acidYield 21.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirring mixture of diisopropylamine (2.2 mL, 15 mmol) and sodium hydride [60% in mineral oil] (0.66 g, 16.5 mmol) in dry THF (50 mL), isobutyric acid (1.4 mL, 15 mmol) was dropwise added. The mixture was refluxed for 15 min, cooled to 0° C., and 2.5M n-butyllithium (BuLi) in hexane (5.45 mL, 14 mmol;) was added. After 20 min at 0° C., the mixture was heated to 30-35° C. for 30 min. The solution was then cooled to 0° C. and (2-bromoethyl)-benzene (2.8 mL, 15 mmol) was slowly added over 20 min. After ca. 1 h at 30-35° C. the reaction was quenched by adding water (40 mL), while keeping the temperature below 15° C. The aqueous layer was separated, and the organic layer washed with a mixture of Et2O/H2O (1:1). The aqueous layers were combined, extracted with Et2O (20 mL), acidified with 2M HCl solution, and the product was further extracted with Et2O (2×30 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under vacuum to afford the title compound (0.619 g, 21%) as a colorless oil. 1H NMR (CDCl3): δ 1.31 (s, 6H), 1.86-1.95 (m, 2H), 2.59-2.68 (m, 2H), 7.17-7.33 (m, 5H).

Workup

  1. additionwas dropwise added
  2. temperatureThe mixture was refluxed for 15 min
  3. temperaturethe mixture was heated to 30-35° C. for 30 min
  4. temperatureThe solution was then cooled to 0° C.
  5. customAfter ca. 1 h at 30-35° C. the reaction was quenched
  6. additionby adding water (40 mL)
  7. customthe temperature below 15° C
  8. customThe aqueous layer was separated
  9. washthe organic layer washed with a mixture of Et2O/H2O (1:1)
  10. extractionextracted with Et2O (20 mL)
  11. extractionthe product was further extracted with Et2O (2×30 mL)
  12. washThe combined organic layers were washed with brine
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-28b7526c5caf46a09dd6d45dda3f30ad
Source dataset
uspto-grants-2016_05
Patent number
US09353075B2

Reaction notes

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