Diisopropylamine → ethyl 3-(4-(benzyloxy)phenyl)-3-hydroxypropanoate

HRID 535273Notes

Reaction equation

HRID 535273 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:16][CH2:17][CH3:18])(=[O:15])[CH3:14].[CH2:19]([O:26][C:27]1[CH:34]=[CH:33][C:30]([CH:31]=[O:32])=[CH:29][CH:28]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1COCC1>[CH2:19]([O:26][C:27]1[CH:28]=[CH:29][C:30]([CH:31]([OH:32])[CH2:14][C:13]([O:16][CH2:17][CH3:18])=[O:15])=[CH:33][CH:34]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 78109Benzaldehyde, 4-(phenylmethoxy)-HCID 178418339Butyllithium

Product 1

HCID 15890182ethyl 3-(4-(benzyloxy)phenyl)-3-hydroxypropanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

23.8 ml of diisopropylamine were initially charged under argon in 250 ml of THF and cooled to 0° C., and 70 ml of n-butyllithium solution (2.5 M in toluene) were added. The mixture was stirred at 0° C. for 30 minutes, then cooled to −75° C., 16.2 ml of ethyl acetate were added slowly and the mixture was stirred for 30 minutes. Then, at −75° C., 30 g of p-benzyloxybenzaldehyde, dissolved in 250 ml of THF, were added dropwise (internal temp. max. −68° C.; 1 h). The mixture was stirred for a further 20 minutes and then the reaction mixture was quenched with 200 ml of sat. NH4Cl solution and 20 ml of 1 N HCl (internal temp. max. −50° C.). The mixture was allowed to thaw to room temperature, the phases were separated and the organic phase was washed three times with 100 ml each time of sat. NH4Cl solution and once with 100 ml of sat. NaCl solution. The solvent was removed under reduced pressure. The residue was extracted by stirring with n-heptane/2% THF and the precipitated solid was filtered off with suction and dried under reduced pressure at 40° C. This gave 41 g of ethyl 3-(4-benzyloxyphenyl)-3-hydroxypropionate as a colorless solid.

Workup

  1. temperaturecooled to −75° C.
  2. stirringthe mixture was stirred for 30 minutes
  3. additionwere added dropwise (internal temp. max. −68° C.; 1 h)
  4. stirringThe mixture was stirred for a further 20 minutes
  5. customthe reaction mixture was quenched with 200 ml of sat. NH4Cl solution and 20 ml of 1 N HCl (internal temp. max. −50° C.)
  6. customthaw to room temperature
  7. customthe phases were separated
  8. washthe organic phase was washed three times with 100 ml each time of sat. NH4Cl solution
  9. customThe solvent was removed under reduced pressure
  10. extractionThe residue was extracted
  11. stirringby stirring with n-heptane/2% THF
  12. filtrationthe precipitated solid was filtered off with suction
  13. customdried under reduced pressure at 40° C

Sources & evidence

ORD record
ord-83517e8ee30049cbbc488a246aef0661
Source dataset
uspto-grants-2014_10
Patent number
US08859494B2

Reaction notes

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