4-Methylmorpholine → HCID 10459847, compound

Participants

Reaction Steps

[(S)-1-(2-Diisopropylamino-ethylcarbamoyl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester. HOBT (1.2 g, 8.49 mmol) and EDCl (1.6 g, 8.49 mmol) were added to a solution of (S)-2-tert-butoxycarbonylamino-3-phenyl-propionic acid in DMF (11 mL). Following the addition of a solution of N′,N′-diisopropyl-ethane-1,2-diamine (0.978 g, 6.8 mmol) in DMF (2 mL), N-methyl-morpholine (1.1 g, 11.3 mmol) was added dropwise. The reaction mixture was stirred at rt overnight. Water (20 mL) and EtOAc (30 mL) were then added to the mixture. The aqueous layer was extracted with EtOAc (3×30 mL). The combined organic layers were washed sequentially with 1 N NaOH (2×20 mL) and brine (40 mL), and dried (MgSO4). The solvents were removed. The crude product was purified by column chromatography [0–20% (1% NH4OH/MeOH)/CH2Cl2] to afford 1.6 g (72%) of the desired product. MS (electrospray): mass calculated for C22H37N3O3, 391.55; m/z found, 392.3 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.57 (s, 1H), 7.36–7.29 (m, 2H), 7.26–7.21 (m, 3H), 3.62–3.55 (m, 1H), 3.49 (d, J=5.5 Hz, 1H), 3.27 (dd, J=4.1, 13.6 Hz, 1H), 3.24 (d, J=6.2 Hz, 1H), 3.22 (d, J=6.1 Hz), 3.02–2.95 (m, 2H), 2.67 (dd, J=13.6, 9.4 Hz, 1H), 2.54 (t, J=6.3 Hz, 2H), 1.67 (s, 1H), 1.24 (d, J=5.6 Hz, 2H), 0.98 (d, J=6.6 Hz, 12H).

Provenance & Evidence