Morpholine → HCID 131732924, compound

Participants

Reaction Steps

Cbz-Asp(O-tBu)-3-(1-naphtyl)-L-alanine-Val-OAllyl (1 g; 1.51 mmol) was co-evaporated with THF to dryness (2*10 ml), then dissolved under argon in dry THF (18 ml, inhibitor free). The solvent was degassed three times under argon (3 min+2+2) before dropwise addition of morpholine (0.658 ml, 5 eq) followed with addition of Tetrakis in one shot (174 mg, 0.1 eq). The mixture was purged under argon for 3 min. the reaction was carried out in the absence of light and at room temperature for 30 minutes. It was then diluted with ether (18 ml) followed with citric acid 0.5M (18 ml). The mixture was stirred for 3 minutes, then extracted. The aqueous layer was washed with ether (3*18 ml) then combined, dried with MgSO4. The solvent was evaporated to dryness. The crude was purified on C-18 column 50 g (pH: 3.5; gradient: 10 to 100° A) MeOH/Water; 4 ml methanol injection volume) to get 0.75 g of the desired product (second pic). NMR 1H (CD3OD, 500 MHz) δ 8.20 (d, 1H, J=8.5 Hz); 7.85 (d, 1H, J=8.1 Hz); 7.75-7.72 (m, 1H); 7.56-7.46 (m, 2H); 7.37-7.27 (m, 7H); 5.09 (q, 2H, J=12.35 Hz); 4.85 (m, 1H); 4.47-4.44 (m, 1H); 4.30 (d, 1H, J=5.8 Hz); 3.68 (dd, 1H, J=14.10; 5.80 Hz); 3.43-3.37 (m, 1H); 2.66 (dd, 1H, J=16.30; 5.9 Hz); 2.46 (dd, 1H, J=16.20; 8.1 Hz); 2.19-2.12 (m. 1H); 1.41 (s, 9H); 0.96 (d, 6H, J=6.80 Hz).

Provenance & Evidence