Reaktion #46747

Reaktionsgleichung

ethanolamine

Cbz-tert-leucine dicyclohexylammonium salt

DIEA

isobutyl chloroformate

→

intermediate 23

(S)-2-amino-N-(2-hydroxyethyl)-3,3-dimethylbutanamide

Lösungsmittel

DCM

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstirred overnight
2. 2
   SonstigeThe reaction was quenched with saturated aqueous sodium bicarbonate
3. 3
   SonstigeThe organic phase was separated
4. 4
   Trocknendried over sodium sulfate
5. 5
   SonstigeAfter evaporation under reduced pressure
6. 6
   workup.DISSOLUTIONthe residue was dissolved in MeOH
7. 7
   Sonstigeto remove dicyclohexylamine and DIEA
8. 8
   SonstigeThe filtrate was evaporated
9. 9
   workup.WAIThydrogenated with Pd/C (0.5 g) under 45 psi hydrogen in MeOH for 4 h
10. 10
    SonstigePalladium catalyst was removed by filtration through celite
11. 11
    EinengenThe filtrate was concentrated
12. 12
    Sonstigedried under vacuum overnight

Vorschrift

To a solution of Cbz-tert-leucine dicyclohexylammonium salt (1.34 g, 3.0 mmol) and DIEA (0.7 ml) in DCM (25 mL) cooled in an ice-water bath was added isobutyl chloroformate (0.47 mL, 3.6 mmol). After stirring at 0° C. for 1 h, ethanolamine was added (0.52 mL, 9.0 mmol) and stirred overnight. The reaction was quenched with saturated aqueous sodium bicarbonate. The organic phase was separated and dried over sodium sulfate. After evaporation under reduced pressure, the residue was dissolved in MeOH and passed through a SCX (Phenomenex®, Torrance, Calif.) cationic ion-exchange column to remove dicyclohexylamine and DIEA. The filtrate was evaporated and hydrogenated with Pd/C (0.5 g) under 45 psi hydrogen in MeOH for 4 h. Palladium catalyst was removed by filtration through celite. The filtrate was concentrated and dried under vacuum overnight to give intermediate 23 (0.35 g), which was used without further purification. LCMS (+ESI) m/z=175 [M+H]+.

Quelle