Hydrochloric Acid → (R)-6-cyano-N,N-diethyl-5-hydroxy-3-oxohexanamide

HRID 1757463Notes

Reaction equation

HRID 1757463 reaction equation
[CH2:1]([N:3]([CH2:7][CH3:8])[C:4](=[O:6])[CH3:5])[CH3:2].C([N-]C(C)C)(C)C.[Li+].[C:17]([CH2:19][C@@H:20]([OH:27])[CH2:21][C:22](OCC)=[O:23])#[N:18].Cl>O1CCCC1.O1CCCC1.CCCCCCC>[C:17]([CH2:19][C@@H:20]([OH:27])[CH2:21][C:22](=[O:23])[CH2:5][C:4]([N:3]([CH2:7][CH3:8])[CH2:1][CH3:2])=[O:6])#[N:18]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 12703N,N-DiethylacetamideHCID 2724682Lithium diisopropylamideHCID 2733879Ethyl (3R)-4-cyano-3-hydroxybutanoate

Product 1

HCID 53728128(R)-6-cyano-N,N-diethyl-5-hydroxy-3-oxohexanamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21263495Tetrahydrofuran heptaneSolvent

Procedure

To a stirred -10° C. solution of N,N-diethylacetamide (prepared fromN,N-diethylamine and acetyl chloride by refluxing for 2 hours in toluene) (28.75 g, 0.25 mol) in tetrahydrofuran (0.25 L) is slowly added a solutionof lithium diisopropylamide in tetrahydrofuran-heptane (0.125 L of 2M) while maintaining the temperature between -10° C. to -5° C.,and the mixture is stirred at -20° C. to 0° C. for 30 minutes. (R)-4-cyano-3-hydroxybutyric acid, ethyl ester (Brower, supra) (10 g, 0.06 mol) as a solution in 200 mL of tetrahydrofuran is added to the previously prepared mixture. The reaction mixture is stirred for 30 minutes at -5° C. to -20° C., and transferred to a 2.2N aqueous hydrochloric acid solution (0.25 L). The aqueous layer is extracted with 300 mL of ethyl acetate, the aqueous layer is separated andreextracted with 50 mL of ethyl acetate, the extracts are combined and concentrated in vacuo to afford crude (R)-6-cyano-N,N-diethyl-5-hydroxy-3-oxohexanamide as an oil; Molecular weight: 226. GC/MS m/e 226, 157, 140, 114, 72, 58, 32.

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 300 mL of ethyl acetate
  4. customthe aqueous layer is separated andreextracted with 50 mL of ethyl acetate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b62efc2575f34cd6a26e68a63e441e49
Source dataset
uspto-grants-1995_08
Patent number
US05446054

Reaction notes

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