Hydrochloric Acid → (+)-3(R)-(2(R)-Amino-3-phenylpropionylamino)-5-cyclohexyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one

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Reaction Conditions

Reaction Steps

3(R,S)-[2(R)-(tert-Butyloxycarbonyl)amino-3-phenylpropio nylamino]-5-cyclohexyl-1,3-dihydro-1-methyl-2H-1,4-benzodiaze pin-2-one (4.7 g, 9.1 mmol) was dissolved in ethyl acetate (20 ml) and cooled to 0° C. This solution was then saturated with hydrogen chloride gas. After 1 h 30 min, the resulting precipitate (which was shown to be the undesired diastereoisomer, Rf =0.04 ethyl acetate), was removed by filtration and the filtrate evaporated. The solid residue was partitioned between ethyl acetate (25m1) and 10% sodium carbonate solution (20 ml). The 25 organic phase was separated and the aqueous extracted with ethyl acetate (2×25 ml). The combined organic phases were dried (Na2SO4) and evaporated in vacuo. The residue was chromatographed on silica using a gradient elution of 0-20% methanol in ethyl acetate to afford the title compound (1.66 g, 44%, Rf =0.13 ethyl acetate) as a pale yellow solid. mp 100-103° C. 1H NMR (360 MHz, CDCl3) δ1.00-1,39 (4H, m), 1.50-1.72 (4H, m), 1.84-1.92 (1H, m), 2.00-2.07 (1H, m), 2.72-2.84 (1H, m), 2.79 (1H, dd, J=13.8 and 9.8 Hz), 3.28 (1H, dd, J=13.8 and 4.0 Hz), 3.40 (3H, s), 3.69 (1H, dd, J=9.8 and 4.1 Hz), 5.36 (1H, d, J=8.3 Hz), 7.21-7.36 (7H, m), 7.47-7.58 (2H, m), 8.66 (1H, d, J=8.3 Hz). [α]23 D +32.7°(c=0.58,CH3OH).

Provenance & Evidence