Isobutyric Acid → 2,2-Dimethyl-3-phenylpropanoic acid

HRID 2108059Notes

Reaction equation

HRID 2108059 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([OH:18])(=[O:17])[CH:14]([CH3:16])[CH3:15].[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>O1CCCC1>[CH3:15][C:14]([CH3:16])([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:13]([OH:18])=[O:17]

Participants

6

Reactant 4

HCID 6590Isobutyric AcidHCID 7498Benzyl BromideHCID 7912DiisopropylamineHCID 178418339Butyllithium

Product 1

HCID 218802,2-Dimethyl-3-phenylpropanoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

To a stirred solution of diisopropylamine (12.6 g, 125 mmol) in tetrahydrofuran (100 ml) under anhydrous conditions at 0° C. was aged n-butyllithium (80.6 ml, 1.55 M in hexane, 125 mmol). The reaction mixture was stirred for 30 minutes at 5° C. and then isobutyric acid (4.4 q, 50 mmol) was added. The reaction mixture was stirred at 0° C. for 30 minutes and then benzyl bromide (17.1 g, 100 mmol) was added dropwise. The reaction mixture was stirred for 2 hours at ambient temperature, quenched with saturated aqueous ammonium chloride (60 ml) and then acidified with 6N hydrochloric acid with cooling. The aqueous phase was saturated with sodium chloride and extracted with diethyl ether (2×100 ml). The combined organic phase was washed with saturated aqueous sodium chloride (2×25 ml) and then dried over magnesium sulfate and concentrated in vacuo to give a viscous oil. The oil was distilled at 0.2 mmHg and the product was collected at 160°-170° C. The product was purified by chromatography on a 5×15 cm column of silica gel eluted with 10 percent diethyl ether/hexane (1 L) and 50 percent diethyl ether/hexane (1 L) to afford the desired product as a colorless solid. m.p. 58°-9° C.

Workup

  1. customat 0° C.
  2. stirringThe reaction mixture was stirred at 0° C. for 30 minutes
  3. stirringThe reaction mixture was stirred for 2 hours at ambient temperature
  4. customquenched with saturated aqueous ammonium chloride (60 ml)
  5. temperaturewith cooling
  6. extractionextracted with diethyl ether (2×100 ml)
  7. washThe combined organic phase was washed with saturated aqueous sodium chloride (2×25 ml)
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated in vacuo
  10. customto give a viscous oil
  11. distillationThe oil was distilled at 0.2 mmHg
  12. customthe product was collected at 160°-170° C
  13. customThe product was purified by chromatography on a 5×15 cm column of silica gel
  14. washeluted with 10 percent diethyl ether/hexane (1 L) and 50 percent diethyl ether/hexane (1 L)

Sources & evidence

ORD record
ord-fcc5fdaa333547468f67b3002aa73773
Source dataset
uspto-grants-1990_06
Patent number
US04937263

Reaction notes

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