1-Hydroxybenzotriazole → {(R)-[4-(2-tert-butoxy-ethoxy)-phenyl]-[(S)-1-(2-fluoro-4-iodo-phenylcarbamoyl)-3,3-dimethyl-butylcarbamoyl]-methyl}-carbamic acid tert-butyl ester

Participants

Reaction Steps

To the solution of 2-amino-4,4-dimethyl-pentanoic acid (2-fluoro-4-iodo-phenyl)-amide (364 mg, 1 mmol), (R)-tert-butoxycarbonylamino-[4-(2-tert-butoxy-ethoxy)-phenyl]-acetic acid (1 M in DMF, 1.1 mL, 1.1 mmol), 1-Hydroxybenzotriazole (168 mg, 1.1 mmol) and diisopropylethyl amine (0.53 mL, 3.3 mmol) in N,N-dimethylformamide (5 mL) was added dropwise the solution of O-benzotriazol-1-yl-N,N,N′,N′-bis(tetramethylene)uronium hexaflurorophosphate (474 mg, 1.1 mmol). The reaction mixture was stirred for 1 hour at room temperature. The reaction mixture was diluted with ethyl acetate and the mixture washed with water and brine. The organic layers were successively washed with 1 M aqueous citric acid solution, brine, saturated aqueous sodium carbonate, brine, dried over sodium sulfate, filtered, and concentrated to give {(R)-[4-(2-tert-butoxy-ethoxy)-phenyl]-[(S)-1-(2-fluoro-4-iodo-phenylcarbamoyl)-3,3-dimethyl-butylcarbamoyl]-methyl}carbamic acid tert-butyl ester (652 mg, 91%) as a white solid.

Provenance & Evidence