1-Hydroxybenzotriazole → {(R)-[4-(2-tert-butoxy-ethoxy)-phenyl]-[(S)-1-(5-iodo-1H-benzoimidazol-2-yl)-2-phenyl-ethylcarbamoyl]-methyl}-carbamic acid tert-butyl ester

Participants

Reaction Steps

To a solution of (S)-1-(5-iodo-1H-benzoimidazol-2-yl)-2-phenyl-ethylamine (161 mg, 0.44 mmol) in N,N-dimethylformamide (3 mL) at 0° C. was added (R)-tert-butoxycarbonylamino-[4-(2-tert-butoxy-ethoxy)-phenyl]-acetic acid (179 mg, 0.49 mmol) (prepared as described below), N,N-diisopropylethylamine (310 μL, 1.77 mmol), N-hydroxybenzotriazole (72 mg, 0.53 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (202 mg, 0.53 mmol) and a catalytic amount of dimethyl-pyridin-4yl-amine. The mixture was stirred under an atmosphere of nitrogen with warming to room temperature over 3 hours. The reaction was poured into ice/water (20 mL) and extracted with ethyl acetate (2×20 mL). The organic extracts were combined, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by chromatography over silica gel gradient eluted with 20 to 35% v/v ethyl acetate/hexanes to give {(R)-[4-(2-tert-butoxy-ethoxy)-phenyl]-[(S)-1-(5-iodo-1H-benzoimidazol-2-yl)-2-phenyl-ethylcarbamoyl]-methyl}-carbamic acid tert-butyl ester (260 mg, 83%).

Provenance & Evidence