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

Temperature

0 °C

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 hour, 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 hydrogen at 45 psi in MeOH for 4 hours. 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]+.

1. stirringstirred overnight
2. customThe reaction was quenched with saturated aqueous sodium bicarbonate
3. customThe organic phase was separated
4. dry with materialdried over sodium sulfate
5. customAfter evaporation under reduced pressure
6. dissolutionthe residue was dissolved in MeOH
7. customto remove dicyclohexylamine and DIEA
8. customThe filtrate was evaporated
9. waithydrogenated with Pd/C (0.5 g) under hydrogen at 45 psi in MeOH for 4 hours
10. customPalladium catalyst was removed by filtration through celite
11. concentrationThe filtrate was concentrated
12. customdried under vacuum overnight

ORD record

ord-70ef04a95bc5467ba072f1a401c5abbb

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653127B2