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

Participants

Reaction Conditions

Reaction Steps

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)+.

Provenance & Evidence