4-Methylmorpholine → (S)-2-((S)-2-tert-Butoxycarbonylamino-3,3-dimethyl-butyrylamino)-propionic acid ethyl ester

Temperatur

-40 °C

To a solution of (S)-2-(tert-butoxycarbonylamino)-3,3-dimethylbutanoic acid (18) (10 g, 43.3 mmol) in THF (100 mL) at −40° C. was added isobutyl chloroformate (5.9 mL, 45.5 mmol) followed by NMM (10.45 mL, 95.23 mmol) and stirred at −40° C. for 1 h. A solution of H-Ala-OMe (7.3 g, 47.6 mmol) in DMF (5 mL) was added to the above reaction mixture and stirred at −40° C. After 2.5 h, EtOAc (500 mL) was added to the reaction mixture, stirred for 10 min and filtered to remove the salts. The filtrate was washed with 10% citric acid (3×100 mL), 5% NaHCO3 solution (3×100 mL), brine solution (100 mL), dried (Na2SO4) and concentrated. The obtained residue was stirred with pet. ether (100 mL) for 30 min, the resulting solid was isolated by filtration to obtain the desired compound (6 g, 43%) as a white solid. Rf: 0.3 (20% EtOAc/pet. ether); 1H NMR (400 MHz, DMSO-d6): 8.3 (1H, d, J=6 Hz), 6.36 (1H, d, J=9.6 Hz), 4.22 (1H, m), 4.1-4.03 (2H, m), 3.89 (1H, d, J=9.6 Hz), 1.38 (9H, s), 1.27 (3H, d, J=7.2 Hz), 1.16 (3H, t, J=6.8 Hz), 0.91 (9H, s); m/z 331 (MH)+.

1. stirringstirred at −40° C
2. waitAfter 2.5 h
3. stirringstirred for 10 min
4. filtrationfiltered
5. customto remove the salts
6. washThe filtrate was washed with 10% citric acid (3×100 mL), 5% NaHCO3 solution (3×100 mL), brine solution (100 mL)
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated
9. stirringThe obtained residue was stirred with pet. ether (100 mL) for 30 min
10. customthe resulting solid was isolated by filtration

ORD-Eintrag

ord-f7346d799295496e8d575775aef92238

Quelldatensatz

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08637453B2