Acetic Acid → 2-Amino-2-[6-(2,2-dimethylpropyl)-1H-benzimidazol-2-yl]propan-1-ol

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Reaction Steps

To a solution of 2-((tert-butoxycarbonyl)amino)-3-hydroxy-2-methylpropanoic acid (Preparation 53, 186 mg, 0.85 mmol) acetonitrile (4.0 mL) and 4-methylmorpholine (0.15 mL, 1.4 mmol) cooled in an ice/brine bath was added isobutylchloroformate (0.050 mL, 0.38 mmol). The mixture was stirred for 30 minutes and then 4-neopentylbenzene-1,2-diamine (Preparation 83, 139 mg, 0.78 mmol) was added. The reaction mixture was allowed to warm to room temperature and stir for 4 days. The solvent was evaporated and the resulting oil was dissolved in acetic acid (3.0 mL, 50 mmol) and stirred at room temperature for 16 hours and then heated to 70° C. for 5 hours. After cooling, the solvent was removed in vacuo and the residue purified by silica gel column chromatography eluting with a 0-100% ethyl acetate/hexanes gradient. The resulting oil was dissolved in methylene chloride (5 mL) and treated with trifluoroacetic acid (0.5 mL, 6 mmol). After stirring for 2 hours, the reaction mixture was concentrated in vacuo and purified by silica gel column chromatography eluting with a 0-100% CMA80/methylene chloride gradient to provide the title compound (20.6 mg, 10%) as an off-white solid.

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