Toluene → benzyl (4S,10aR)-1,5-dioxodecahydropyrido[1,2-a][1,4]diazepin-4-ylcarbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-methyl 1-((S)-3-amino-2-(benzyloxycarbonylamino)propanoyl)piperidine-2-carboxylate trifluoroacetate (601 mg, 1.26 mmol) in ClCH2CH2Cl (10 mL) at rt was added trimethylaluminum in toluene (1.89 mL, 3.78 mmol). The reaction was stirred in a sealed bottle at 75° C. for 3 days. After cooling to rt, the reaction was quenched with water and then aqueous 1 N HCl solution until the solution became clear. The aqueous solution was extracted with DCM (2×30 mL). The combined organic layers were washed with saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 50-100% EtOAc/Hex to give benzyl (4S,10aR)-1,5-dioxodecahydropyrido[1,2-a][1,4]diazepin-4-ylcarbamate (71 mg, 0.21 mmol, 17% yield) as a white solid. Anal. Calcd. for C17H21N3O4 m/z 331.4. found: 332.3 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 7.65-7.02 (m, 5H), 6.20 (d, J=5.5 Hz, 1H), 5.59 (s, 1H), 5.35-4.96 (m, 2H), 4.58 (s, 1H), 4.15 (d, J=13.3 Hz, 1H), 3.99-3.70 (m, 1H), 3.26-2.82 (m, 2H), 2.46-2.14 (m, 1H), 1.93-1.37 (m, 6H).

Provenance & Evidence