Hydrochloric Acid → (1-{2-[5-(6-Bromonaphthalen-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

Participants

Reaction Steps

To 2-[5-(6-Bromo-naphthalen-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (6.4 g, 14.4 mmol) was added HCl in dioxane (36 mL, 144 mmol). The suspension was allowed to stir at room temperature for three hours. Upon completion by LCMS, the reaction was concentrated to dryness and the crude product (assumed 14.4 mmol) was suspended in dichloromethane. 2-Methoxycarbonylamino-3-methylbutyric acid (3.8 g, 21.7 mmol) and solid potassium phosphate (28.94 mmol) were added to the slurry. HATU (6.88 g, 18.08 mL) was added and the reaction was stirred at room temperature for 18 hours. Upon completion, the crude reaction was filtered through a sintered glass funnel. The supernate was concentrated in vacuo and purified by normal phase silica gel chromatography (20-70% Ethyl acetate (with 10% MeOH) in Hexanes) to give (1-{2-[5-(6-Bromo-naphthalen-2-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (7.14 g, >90% yield) as a thick oil. LCMS-ESI+: calc'd for C24H27BrN4O3: 498.13 (M+); Found: 499.96 (M+H+).

Provenance & Evidence