Acetic Acid → (S)-tert-butyl (1-(5-bromo-1H-benzo[d]imidazol-2-yl)-3-oxo-3-(tritylamino)propyl)carbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of Boc-Asn(Trt)-OH (1.05 g, 2.21 mmol) in anhydrous tetrahydrofuran (4 mL) cooled in an ice water bath was added 4-methylmorpholine (0.365 mL, 3.32 mmol) and isobutyl chloroformate (0.316 mL, 2.43 mmol). The reaction mixture was stirred for 1 hour at 0° C. and then 4-bromo-1,2-benzenediamine (414 mg, 2.21 mmol) was added. The reaction mixture was allowed to warm to room temperature over 2 hours and then stirred an additional 2 hours. The reaction mixture was concentrated in vacuo and dried. To the resulting residue was added acetic acid (12 mL, 210 mmol) and the mixture stirred at 65° C. for 2 hours. The reaction was concentrated in vacuo and the residue taken up in ethyl acetate, washed with water, saturated aqueous sodium hydrogen carbonate solution, and brine. The organic layer was dried over anhydrous magnesium sulphate, filtered, and concentrated in vacuo to give crude product that was purified by silica gel column chromatography eluting with a 0-100% ethyl acetate/methylene chloride gradient. This provided the title compound (1.38 g, 61%) as a light tan solid.

Provenance & Evidence