Diisopropylamine → Diethyl 3-(4-t-butyldimethylsilyloxybenzyl)-2-ethyl-2-hydroxysuccinate

HRID 1774376Notes

Reaction equation

HRID 1774376 reaction equation
C(NC(C)C)(C)C.[Si:8]([O:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:18][CH:17]=1)([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9].[O:29]=[C:30]([CH2:36][CH3:37])[C:31]([O:33][CH2:34][CH3:35])=[O:32].CCCCCC.C(OCC)(=O)C>O1CCCC1>[Si:8]([O:15][C:16]1[CH:17]=[CH:18][C:19]([CH2:22][CH:23]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:30]([CH2:36][CH3:37])([OH:29])[C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:20][CH:21]=1)([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 85195ethyl acetoacetate, sodium saltHCID 11500531Ethyl 3-(4-t-butyldimethylsilyloxyphenyl)propionateHCID 21226206Ethyl acetate hexane

Product 1

HCID 66648734Diethyl 3-(4-t-butyldimethylsilyloxybenzyl)-2-ethyl-2-hydroxysuccinateYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

Under the atmosphere of argon, to a solution of diisopropylamine (572 mg, 5.65 mmol) in anhydrous tetrahydrofuran (7 mL) was added a 1.54 M n-butyl lithium-hexane solution (3.5 mL, 5.4 mmol) with stirring under ice cooling, and the mixture was stirred at 0° C. for 10 min and then at −78° C. for 5 min. To the mixture, a solution of ethyl 3-(4-t-butyldimethylsilyloxyphenyl)propionate (1.47 g, 4.78 mmol) in anhydrous tetrahydrofuran (7 mL) was added dropwise at the same temperature over 6 min, and the reaction mixture was further stirred for 20 min. The cold solution of the enolate thus prepared above was added dropwise via a cannula into a solution of ethyl 2-ketobutyrate (518 mg, 3.98 mmol) in anhydrous tetrahydrofuran (5 mL) having been cooled to −78° C. After stirring at −78° C. for 1 h, the reaction mixture was quenched and adjusted to pH 4 with acetic acid, and the temperature was raised to room temperature. The reaction solvent was evaporated under reduced pressure, and the residue was diluted with ethyl acetate and water to separate the phases. The organic layer having been washed with brine was concentrated under reduced pressure. The residue obtained was subjected to silica gel column chromatography (hexane-ethyl acetate 10:1→5:1) to give diethyl 3-(4-t-butyldimethylsilyloxybenzyl)-2-ethyl-2-hydroxysuccinate as oil in amounts of 433 mg (low polar diastereomer, yield: 25%) and 290 mg (high polar diastereomer, yield: 17%), respectively.

Workup

  1. stirringthe mixture was stirred at 0° C. for 10 min
  2. stirringthe reaction mixture was further stirred for 20 min
  3. stirringAfter stirring at −78° C. for 1 h
  4. customthe reaction mixture was quenched
  5. temperaturethe temperature was raised to room temperature
  6. customThe reaction solvent was evaporated under reduced pressure
  7. additionthe residue was diluted with ethyl acetate and water
  8. customto separate the phases
  9. washThe organic layer having been washed with brine
  10. concentrationwas concentrated under reduced pressure
  11. customThe residue obtained

Sources & evidence

ORD record
ord-9391814a821a463e88c0d90f92890e82
Source dataset
uspto-grants-2016_02
Patent number
US09260375B2

Reaction notes

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