1,2-Dichloroethane → Ethyl 3-((R)-1-benzyl-5-oxopyrrolidine-2-carboxamido)-2-hydroxy-4-phenylbutanoate

HRID 882841Notes

Reaction equation

HRID 882841 reaction equation
[CH2:1]([N:8]1[C:12](=[O:13])[CH2:11][CH2:10][C@@H:9]1[C:14]([OH:16])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.[NH2:27][CH:28]([CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[CH:29]([OH:35])[C:30]([O:32][CH2:33][CH3:34])=[O:31].C(Cl)CCl.CCN(C(C)C)C(C)C>C1COCC1.CN(C=O)C>[CH2:1]([N:8]1[C:12](=[O:13])[CH2:11][CH2:10][C@@H:9]1[C:14]([NH:27][CH:28]([CH2:36][C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1)[CH:29]([OH:35])[C:30]([O:32][CH2:33][CH3:34])=[O:31])=[O:16])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 18690978Ethyl 3-amino-2-hydroxy-4-phenylbutanoateHCID 23390401HCID 23390401, compound

Product 1

HCID 66644659Ethyl 3-((R)-1-benzyl-5-oxopyrrolidine-2-carboxamido)-2-hydroxy-4-phenylbutanoate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (R)-1-benzyl-5-oxopyrrolidine-2-carboxylic acid (2440 mg, 11.13 mmol) in a mixture of 24 ml THF and 4 ml DMF were successively added at 5° C. 1-hydroxybenzotriazole (1875 mg, 12.24 mmol), ethyl 3-amino-2-hydroxy-4-phenylbutanoate (2485 mg, 11.13 mmol; preparation described in WO 98/25883, example 8a on page 24), EDC (2347 mg, 12.24 mmol) and DIPEA (6.41 mL; 4750 mg, 36.7 mmol). After stirring overnight at room temperature the reaction mixture was concentrated under reduced pressure, water was added and the obtained mixture was extracted three times with ethyl acetate. The organic layer was washed successively with aq. saturated NaHCO3 (2×), 10% aq. citric acid solution (3×) and brine, dried over Na2SO4 and the solvent was then removed under reduced pressure. The title compound was obtained as a yellow oil (4550 mg, yield: 96%), which was used without further purification in the next step.

Workup

  1. additionwere successively added at 5° C
  2. concentrationwas concentrated under reduced pressure, water
  3. additionwas added
  4. extractionthe obtained mixture was extracted three times with ethyl acetate
  5. washThe organic layer was washed successively with aq. saturated NaHCO3 (2×), 10% aq. citric acid solution (3×) and brine
  6. dry with materialdried over Na2SO4
  7. customthe solvent was then removed under reduced pressure

Sources & evidence

ORD record
ord-0c4b3c7ea786478e8255a9516cbe83ed
Source dataset
uspto-grants-2012_08
Patent number
US08236798B2

Reaction notes

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