Hydrochloric Acid → (R)-epsilon-hydroxy-alpha,gamma-dioxo-1-piperidineheptanenitrile

To a stirred -10° C. solution of 1-acetylpiperidine (127 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 -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) (40 g, 0.25 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 (1L). The aqueous layer is extracted with 500 mL of ethyl acetate, the aqueous layer is separated and extracted with 100 mL of ethyl acetate, the extracts are combined and concentrated in vacuo to afford (R)-ε-hydroxy-α,γ-dioxo -1-piperidineheptanenitrile 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 500 mL of ethyl acetate
4. customthe aqueous layer is separated
5. extractionextracted with 100 mL of ethyl acetate
6. concentrationconcentrated in vacuo

ORD record

ord-b81e77367b664530bd0f55195eb2ca42

Source dataset

uspto-grants-1996_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05489690