Hydrochloric Acid → (R)-N-butyl-6-cyano-5-hydroxy-N-methyl-3-oxohexanamide

To a stirred -10° C. solution of N,N-n-butylmethylacetamide (prepared from N,N-n-butylmethylamine and acetyl chloride by refluxing for 2hours in toluene) (65 g, 0.5 mol) in tetrahydrofuran (0.5 L) is slowly added a solution of lithium diisopropylamide in tetrahydrofuran-heptane (0.25 L of 2M) while maintaining the temperature between -40° C. to -50° C., and the mixture is stirred at -20° C. to -30° C. for 30 minutes. (R)-4-cyano-3-hydroxybutyric acid, ethyl ester (Brower, supra) (20 g, 0.125 mol) as a solution in 200 mL of tetrahydrofuran is then added to the previous mixture. The reaction mixture is stirred for 30 minutes at -25° C. to -20° C., and transferred to a 2.2N aqueous hydrochloric acid solution (0.5 L). The aqueous layer is extracted with 300 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)-N-butyl-6-cyano-5-hydroxy-N-methyl-3-oxohexanamide as an oil.

1. temperaturewhile maintaining the temperature between -40° C. to -50° C.
2. stirringThe reaction mixture is stirred for 30 minutes at -25° C. to -20° C.
3. extractionThe aqueous layer is extracted with 300 mL of ethyl acetate
4. customthe aqueous layer is separated
5. concentrationconcentrated in vacuo

ORD record

ord-73883e07f1c0431cbca6946b58184cdd

Source dataset

uspto-grants-1996_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05510488