Ethyl ethoxyacetate → 3-(4-Benzyloxy-2-methyl-phenyl)-2-ethoxy-3-hydroxy-propionic acid ethyl ester

HRID 1394670Notes

Reaction equation

HRID 1394670 reaction equation
C([N-]C(C)C)(C)C.[Li+].[CH2:9]([O:11][C:12](=[O:17])[CH2:13][O:14][CH2:15][CH3:16])[CH3:10].[CH2:18]([O:25][C:26]1[CH:33]=[CH:32][C:29]([CH:30]=[O:31])=[C:28]([CH3:34])[CH:27]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C1COCC1.CCCCCCC.O1CCCC1>[CH2:9]([O:11][C:12](=[O:17])[CH:13]([O:14][CH2:15][CH3:16])[CH:30]([C:29]1[CH:32]=[CH:33][C:26]([O:25][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:27][C:28]=1[CH3:34])[OH:31])[CH3:10]

Participants

6

Reactant 3

HCID 69955Ethyl ethoxyacetateHCID 2724682Lithium diisopropylamideHCID 27598062-Methyl 4-benzyloxybenzaldehyde

Product 1

HCID 692799043-(4-Benzyloxy-2-methyl-phenyl)-2-ethoxy-3-hydroxy-propionic acid ethyl esterYield 102.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21263495Tetrahydrofuran heptaneSolvent

Procedure

To a −78° C. cold 2 M solution of lithium diisopropylamide (305 mmol) in THF/n-heptane (152.4 ml) was added a solution of ethoxy-acetic acid ethyl ester (45.2 ml, 331 mmol) in tetrahydrofuran (240 ml) within 1.5 h under an argon atmosphere. The mixture was stirred for 30 min. A solution of 4-benzyloxy-2-methyl-benzaldehyde (30 g, 132.6 mmol) in tetrahydrofuran (420 ml) was added dropwise over a period of 50 min. The reaction mixture was stirred 2 h at −78° C., poured onto ice water/aqueous ammonium chloride solution 1/1 and extracted two times with ethyl acetate. The combined extracts were washed three times with ice water/brine 1/1 and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue purified by column chromatography (silica gel, n-heptane/AcOEt) to give 48.8 g (136.2 mmol) of the title compound as a mixture of stereoisomers as yellow oil.

Workup

  1. stirringThe reaction mixture was stirred 2 h at −78° C.
  2. additionpoured onto ice water/aqueous ammonium chloride solution 1/1
  3. extractionextracted two times with ethyl acetate
  4. washThe combined extracts were washed three times with ice water/brine 1/1
  5. dry with materialdried over sodium sulfate
  6. customThe solvent was removed under reduced pressure
  7. customthe residue purified by column chromatography (silica gel, n-heptane/AcOEt)

Sources & evidence

ORD record
ord-996326a4985549389dc0bb98233c6787
Source dataset
uspto-grants-2008_03
Patent number
US07348349B2

Reaction notes

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