Reaktion #217131

Reaktionsgleichung

hydrochloric acid

(R)-4-cyano-3-hydroxybutyric acid, ethyl ester

tetrahydrofuran

N-phenylmethylacetamide

lithium diisopropylamide

tetrahydrofuran

→

(R)-6-cyano-N-(1,1-dimethylethyl)-5-hydroxy-3-oxo-N-(phenylmethyl)hexanamide

Lösungsmittel

tetra-hydrofuran heptane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwhile maintaining the temperature between -40° C. to -50° C.
2. 2
   workup.STIRRINGThe reaction mixture is stirred for 30 minutes at -25° C. to -20° C.
3. 3
   ExtraktionThe aqueous layer is extracted with 300 mL of ethyl acetate
4. 4
   Sonstigethe aqueous layer is separated
5. 5
   Einengenconcentrated in vacuo

Vorschrift

To a stirred -10° C. solution of N-1,1-dimethylethyl, N-phenylmethylacetamide (prepared from N-1,1-dimethylethyl, N-phenylmethyl amine, and acetyl chloride by refluxing for 2 hours in toluene) (102.5 g, 0.5 mol) in tetrahydrofuran (0.5 L) is slowly added a solution of lithium diisopropylamide in tetra-hydrofuran-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 or 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)-6-cyano-N-(1,1-dimethylethyl)-5-hydroxy-3-oxo-N-(phenylmethyl)hexanamide as an oil.

Quelle