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

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Reaction Steps

A solution of 5-cyclohexyl-1,3-dihydro-3(R,S)-[ (benzyloxycarbonyl)amino]-2H-1,4-benzodiazepin-2-one(7.0 g, 18 mmol)in dimethylformamide (84 ml), under an atmosphere of nitrogen, was treated with sodium hydride (0.77 g of a 55-60% dispersion in mineral oil, 18 mmol) in one portion, at -10° C. After 30 min at -10° C., 1-iodo-2-methylpropane (2.3 ml, 19.8 mmol) was added in one portion and the solution allowed to reach 0° C. over 2 h, then stirred at ambient temperature overnight. After this time the solvent was removed under reduced pressure, and the crude residue partitioned between water (500 ml) and dichloromethane (500 ml). The organic phase was separated and the aqueous phase extracted with dichloromethane (2×500 ml). The combined organic layers were washed with brine (500 ml), dried (MgSO4) and evaporated in vacuo. The residue was chromatographed on silica gel, using 2:1 petrol:ethyl acetate as the eluant, to afford the title compound (4.5 g, 56%) as a white solid. mp 148°-150° C. 1H NMR (360 MHz, CDCl3) δ 0.73 (3H, d, J=7 Hz), 0.79 (3H, d, J=7 Hz), 1.14-2.09 (11H, m), 2.80 (1H, m), 3.42 (1H, dd, J=14 and 5 Hz), 4.27 (1H, dd, J=14 and 9 Hz), 5.10 (3H, m), 6.55 (1H, d, J=8 Hz), 7.23-7.34 (8H, m), 7.45 (1H, t, J=8 Hz), 7.56 (1H, d, J=8 Hz).

Provenance & Evidence