Hydrochloric Acid → Cyclohexyl-[5,6-difluoro-2-((S)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-acetic acid

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Reaction Steps

To a solution of N-benzyl-2-cyclohexyl-2-[5,6-difluoro-2-((S)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-acetamide (2.16 g, 4 mmol, 1.0 equiv) in acetonitrile (25 ml) were added di-tert.-butyl-dicarbonate (1.123 g, 5 mmol, 1.2 equiv., [CAS RN 24424-99-5]) and N,N-dimethylaminopyridine ((0.051 g, 0.1 equiv., [CAS RN 1122-58-3]). The mixture was stirred 48 h at room temperature. A solution of lithium hydroxide monohydrate (0.54 g, 3.0 equiv., [CAS RN 1310-66-3]) in water (4 ml) was added, and the mixture vigorously stirred overnight at room temperature, and 2 h at 70° C. The mixture was allowed to cool to room temperature and poured into 1M aqueous hydrochloric acid (25 ml). The product was extracted with ethyl acetate (3×50 ml) and the combined organic phases washed with brine and dried over magnesium sulfate. The brown residue was purified by column chromatography on silica gel (75 g, 1:0 to 98:2 EtOAc/AcOH eluant) to afford the product as an off-white mixture of diastereomers. MS (ISN): 413.1 [M−H]−.

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