1,2-Dichloroethane → (2R,5R)-methyl 2,5-dibenzyl-6-oxo-6-((R)-2-oxo-1-phenylazepan-3-ylamino)hexanoate

Participants

Reaction Steps

To a round bottom flask was added (2R,5R)-2,5-dibenzyl-6-methoxy-6-oxohexanoic acid (278 mg, 0.817 mmol), (S)-3-amino-1-phenylazepan-2-one trifluoroacetic acid salt (260 mg, 0.817 mmol), HOBT (163 mg, 1.062 mmol), EDC (204 mg, 1.062 mmol), Hunig's base (317 mg, 2.45 mmol) and DMF (5 mL). The reaction was stirred at rt for 2 days. The reaction mixture was partitioned between EtOAc and water. The organic phase was isolated, washed with aqueous 0.5 N HCl, saturated aqueous NaHCO3 and saturated aqueous NaCl. The organic phase was then dried over MgSO4, filtered and concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 30-60% EtOAc/Hex to give (2R,5R)-methyl 2,5-dibenzyl-6-oxo-6-((R)-2-oxo-1-phenylazepan-3-ylamino)hexanoate (305 mg, 0.579 mmol, 70.9% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.38 (t, J=7.7 Hz, 2H), 7.32-7.20 (m, 5H), 7.20-7.06 (m, 8H), 6.75 (d, J=6.2 Hz, 1H), 4.70 (dd, J=10.0, 6.3 Hz, 1H), 3.90 (dd, J=15.3, 11.4 Hz, 1H), 3.67-3.47 (m, 4H), 2.95-2.82 (m, 2H), 2.77-2.57 (m, 3H), 2.43-2.30 (m, 1H), 2.02-1.78 (m, 3H), 1.77-1.39 (m, 5H), 1.35-1.20 (m, 2H).

Provenance & Evidence