Isobutyl iodide → 1,3-dihydro-1-(2-methylpropyl)-5-(2-propyl)-3(R,S)-[(benzyloxycarbonyl)-amino]-2H-1,4-benzodiazepin-2-one

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Reaction Steps

A solution of 1,3-dihydro-5-(2-propyl)-3(R,S)-[(benzyloxycarbonyl)-amino]-2H-1,4-benzodiazepin-2-one (500 mg, 1.42 mmol) in dimethylformamide (10 ml) under an atmosphere of nitrogen, was treated with sodium hydride (57 mg of a 57% dispersion in mineral oil, 1.42 mmol) in one portion at 0° C. After 1 h, 2-methylpropyl iodide (0.17 ml, 1.50 mmol) was added and the resulting mixture was stirred at room temperature for 16 h. The solvent was then evaporated and the crude residue partitioned between water (15 ml) and dichloromethane (2×20 ml). The combined organic phase was washed with brine (20 ml), dried (MgSO4) and evaporated. The residue was chromatographed on silica using 1:3 ethyl acetate:petrol as eluent, to afford 1,3-dihydro-1-(2-methylpropyl)-5-(2-propyl) -3(R,S)-[(benzyloxycarbonyl)-amino]-2H-1,4-benzodiazepin-2-one (530 mg, 92%) as a colourless solid. 1H NMR (250 MHz, CDCl3) δ 0.72 (3H, d, J=8 Hz), 0.80 (3H, d, J =8 Hz), 1.02 (3H, d, J=7 Hz), 1.30 (3H, d, J=7 Hz), 1.64 (1H, m), 3.10 (1H, m), 3.42 (1H, dd, J=15 Hz, 5 Hz), 4.30 (1H, dd, J=12.5 Hz, J=7.5 Hz), 5.12 (3H, m), 6.55 (1H, d, J=10 Hz), 7.10-7.70 (9H, m).

Provenance & Evidence