Ethyl propoxyacetate → 3-hydroxy-2-propoxy-3-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-indol-5-yl]-propionic acid ethyl ester

HRID 2181189Notes

Reaction equation

HRID 2181189 reaction equation
[Li].C([N-]C(C)C)(C)C.[CH2:9]([O:11][C:12](=[O:18])[CH2:13][O:14][CH2:15][CH2:16][CH3:17])[CH3:10].[CH3:19][Si:20]([CH3:37])([CH3:36])[CH2:21][CH2:22][O:23][CH2:24][N:25]1[C:33]2[C:28](=[CH:29][C:30]([CH:34]=[O:35])=[CH:31][CH:32]=2)[CH:27]=[CH:26]1>O1CCCC1>[CH2:9]([O:11][C:12](=[O:18])[CH:13]([O:14][CH2:15][CH2:16][CH3:17])[CH:34]([OH:35])[C:30]1[CH:29]=[C:28]2[C:33](=[CH:32][CH:31]=1)[N:25]([CH2:24][O:23][CH2:22][CH2:21][Si:20]([CH3:36])([CH3:19])[CH3:37])[CH:26]=[CH:27]2)[CH3:10]

Participants

5

Reactant 3

HCID 21910278Ethyl propoxyacetateHCID 224856951-(2-Trimethylsilylethyl)oxymethylindole-5-carboxaldehydeHCID 86591433Lithium di-isopropylamide

Product 1

HCID 695629283-hydroxy-2-propoxy-3-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-indol-5-yl]-propionic acid ethyl esterYield 91.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a solution of 30 mmol lithium-diisopropylamide in 50 ml tetrahydrofuran were added at −78° C. 4.39 g propoxy-acetic acid ethyl ester [Journal of the American Chemical Society (1996), 118(41), 9901-9907] dissolved in 25 ml of tetrahydrofuran; after 30 min. stirring at −78° C., a solution of 3.31 g 1-(2-trimethylsilanyl-ethoxymethyl)-1H-indole-5-carbaldehyde in 30 ml tetrahydrofuran was added and after another 30 min., the reaction mixture was quenched with 25 ml H2O and then warmed up to ambient temperature. It was then extracted with ethyl acetate and the combined organic phases were washed with water, dried over magnesium sulfate and evaporated to give a light brown oil which was purified by chromatography (silicagel, eluent: gradient of n-heptane/EtOAc) to yield 4.65 g 3-hydroxy-2-propoxy-3-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-indol-5-yl]-propionic acid ethyl ester (mixture of diasteromers) as a yellow oil.

Workup

  1. customthe reaction mixture was quenched with 25 ml H2O
  2. temperaturewarmed up to ambient temperature
  3. extractionIt was then extracted with ethyl acetate
  4. washthe combined organic phases were washed with water
  5. dry with materialdried over magnesium sulfate
  6. customevaporated
  7. customto give a light brown oil which
  8. customwas purified by chromatography (silicagel, eluent: gradient of n-heptane/EtOAc)

Sources & evidence

ORD record
ord-119009cca78a4641bbdf91fe2e53e5e9
Source dataset
uspto-grants-2005_05
Patent number
US06890947B2

Reaction notes

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