Hydrochloric Acid → (R)-6-cyano-5-hydroxy-3-oxo-N,N-diphenylhexanamide

HRID 2395892Notes

Reaction equation

HRID 2395892 reaction equation
[C:1]1([N:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:8](=[O:10])[CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([N-]C(C)C)(C)C.[Li+].[C:25]([CH2:27][C@@H:28]([OH:35])[CH2:29][C:30](OCC)=[O:31])#[N:26].Cl>O1CCCC1.O1CCCC1.CCCCCCC>[C:25]([CH2:27][C@@H:28]([OH:35])[CH2:29][C:30](=[O:31])[CH2:9][C:8]([N:7]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)=[O:10])#[N:26]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10615N,N-DiphenylacetamideHCID 2724682Lithium diisopropylamideHCID 2733879Ethyl (3R)-4-cyano-3-hydroxybutanoate

Product 1

HCID 9818592(R)-6-cyano-5-hydroxy-3-oxo-N,N-diphenylhexanamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21263495Tetrahydrofuran heptaneSolvent

Procedure

To a stirred -10° C. solution of N,N-diphenylacetamide (211 g, 1.0 mol) in tetrahydrofuran (1.0 L) is slowly added a solution of lithium diisopropylamide in tetrahydrofuran-heptane (0.5 L of 2M) while maintaining the temperature between -10° C. to -5° C. The mixture is stirred at -0° C. to 20° C. for 30 minutes. (R)-4-cyano-3-hydroxybutyric acid, ethyl ester (Brower, supra) (40 g, 0.25 mol) as a solution in 200 mL of tetrahydrofuran is added to the previously prepared anion. The reaction mixture is stirred for 30 minutes at -5° C. to -20° C., and transferred to a 2.2N aqueous hydrochloric acid solution (1 L). The aqueous layer is extracted with 500 mL of ethyl acetate, the aqueous layer is separated and reextracted with 100 mL of ethyl acetate, the extracts are combined and concentrated in vacuo to afford crude (R)-6 -cyano-5-hydroxy-3-oxo-N,N-diphenylhexanamide which is not isolated. A small sample is purified by column chromatography on flash silica gel (60:40 hexane:ethyl acetate) as an oil. Proton nuclear magnetic resonance spectroscopy

Workup

  1. temperaturewhile maintaining the temperature between -10° C. to -5° C
  2. stirringThe reaction mixture is stirred for 30 minutes at -5° C. to -20° C.
  3. extractionThe aqueous layer is extracted with 500 mL of ethyl acetate
  4. customthe aqueous layer is separated
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7c34fe9b70a94c258cfa4d699d1a0de1
Source dataset
uspto-grants-1996_02
Patent number
US05489691

Reaction notes

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