Acetic Acid → 3-[2-(4-Benzyloxy-phenyl)ethyl]-3-hydroxy-4-methyl-pentanoic acid tert-butyl ester

HRID 1003880Notes

Reaction equation

HRID 1003880 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])(=[O:15])[CH3:14].[CH2:21]([O:28][C:29]1[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][C:37](=[O:41])[CH:38]([CH3:40])[CH3:39])=[CH:31][CH:30]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(O)(=O)C>C1COCC1>[C:17]([O:16][C:13](=[O:15])[CH2:14][C:37]([CH2:36][CH2:35][C:32]1[CH:33]=[CH:34][C:29]([O:28][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:30][CH:31]=1)([OH:41])[CH:38]([CH3:39])[CH3:40])([CH3:20])([CH3:19])[CH3:18]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 7912DiisopropylamineHCID 10908tert-Butyl acetateHCID 187986371-(4-(Benzyloxy)phenyl)-4-methylpentan-3-oneHCID 178418339Butyllithium

Product 1

HCID 539460993-[2-(4-Benzyloxy-phenyl)ethyl]-3-hydroxy-4-methyl-pentanoic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-40 °C

Procedure

Diisopropylamine (44.8 mL, 320 mmol) in THF (125 mL) was cooled to -15° C. n-Butyllithium (1.6 M, 200 mL, 320 mmol) was added over 20 minutes. The solution was cooled to -40° C. and stirred for 20 minutes. Tert-butyl acetate (43 mL, 320 mmol) in THF (90 mL) was added over 30 minutes and the reaction stirred for 30 minutes at -40° C. 1-(4-Benzyloxy-phenyl)-4-methyl-pentan-3-one (21.0 g, 100 mmol) from Example F in THF (125 mL) was added over 10 minutes and the reaction was stirred at -40° C. for 5 minutes. Acetic acid (40 mL, 700 mmol) was added and the reaction warmed to room temperature. The reaction was stripped to dryness and the product was partitioned between ethyl acetate and saturated NH4Cl. The organic layer was washed with water, 5% NaHCO3 and brine. It was dried (MgSO4) and concentrated to give the title compound.

Workup

  1. additionwas added over 20 minutes
  2. stirringthe reaction stirred for 30 minutes at -40° C
  3. stirringthe reaction was stirred at -40° C. for 5 minutes
  4. temperaturethe reaction warmed to room temperature
  5. customthe product was partitioned between ethyl acetate and saturated NH4Cl
  6. washThe organic layer was washed with water, 5% NaHCO3 and brine
  7. dry with materialIt was dried (MgSO4)
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-b8806cd754fe4d5fa18acdb7e05eb1f3
Source dataset
uspto-grants-2000_04
Patent number
US06046355

Reaction notes

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