反応 #46747

反応方程式

ethanolamine

Cbz-tert-leucine dicyclohexylammonium salt

DIEA

isobutyl chloroformate

→

intermediate 23

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

溶媒

DCM

反応条件

後処理

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

実験手順

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]+.

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