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

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Reaction Steps

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.

Provenance & Evidence