Acetic Acid → HCID 66648766, compound

HRID 1774380Notes

Reaction equation

HRID 1774380 reaction equation
C(NC(C)C)(C)C.[C:8]1([CH2:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[O:21]=[C:22]([CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:23]([O:25][CH2:26][CH3:27])=[O:24].C(O)(=O)C>O1CCCC1.CCCCCC.C(OCC)(=O)C>[CH2:14]([CH:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:22]([CH2:28][CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)([OH:21])[C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 7912DiisopropylamineHCID 16237Ethyl 3-phenylpropionateHCID 562087Ethyl alpha-oxobenzenebutanoate

Product 1

HCID 66648766HCID 66648766, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
-78 °C

Procedure

Diisopropylamine (1.44 g, 14.3 mmol) was dissolved in anhydrous tetrahydrofuran (20 mL) under the atmosphere of argon, and a 1.54 M n-butyl lithium-hexane solution (8.8 mL, 13.6 mmol) was added with stirring under ice cooling. 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-phenylpropionate (2.14 g, 12.0 mmol) in anhydrous tetrahydrofuran (2 mL) was added 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-oxo-4-phenylbutyrate (2.05 g, 10 mmol) in anhydrous tetrahydrofuran (10 mL) having been cooled to −78° C. After stirring at −78° C. for 1 h, the reaction mixture was 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) to give diethyl 3-benzyl-2-phenethyl-2-hydroxysuccinate as oil in amounts of 806 mg (low polar diastereomer, yield: 21%) and 412 mg (high polar diastereomer, yield: 13%), respectively.

Workup

  1. additiona 1.54 M n-butyl lithium-hexane solution (8.8 mL, 13.6 mmol) was added
  2. stirringThe mixture was stirred at 0° C. for 10 min
  3. stirringthe reaction mixture was further stirred for 20 min
  4. stirringAfter stirring at −78° C. for 1 h
  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-d54f927cad214117b7781ab8b2df6511
Source dataset
uspto-grants-2016_02
Patent number
US09260375B2

Reaction notes

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