Boc-D-phenylalanine → 3(R,S)-[2(R)-(tert-butyloxycarbonyl)amino-3-phenylpropionylamino]-5-cycloheptyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one

Participants

Reaction Steps

To a solution of 3(R,S)-amino-5-cycloheptyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one (4.08 g) in anhydrous dimethyl formamide (30 ml), under an atmosphere of nitrogen, was added in succession Boc-D-phenylalanine (3.98 g), 1-hydroxybenzotriazole trihydrate (2.03 g) and 1-ethyl-3-[3-(dimethylamino)propyl] carbodiimide hydrochloride (2.88 g). Triethylamine (2.09 ml) was then added and the resulting suspension stirred at ambient temperature for 1 h. The solvent was removed under reduced pressure and the residue partitioned between ethyl acetate (100 ml) and 10% citric acid solution (100 ml). The organic phase was separated and the aqueous phase extracted with ethyl acetate (3×50 ml). The combined organic phases were washed with 10% sodium hydroxide solution (100 ml), water (50 ml) and brine (50 ml). The organic layer was separated, dried (Na2SO4) and evaporated in vacuo to afford crude 3(R,S)-[2(R)-(tert-butyloxycarbonyl)amino-3-phenylpropionylamino]-5-cycloheptyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one.

Provenance & Evidence