2-Methylbenzenesulfonamide → 3-[(4-{Hydroxy[(2-methylbenzene-1-sulfonyl)imino]methyl}-2-methoxyphenyl)methyl]-1-methyl-N-(4,4,4-trifluoro-2-methylbutyl)-1H-indole-5-carboximidic acid

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A mixture of (R)-3-methoxy-4-[1-methyl-5-(2-methyl-4,4,4-trifluorobutylcarbamoyl)indol-3-ylmethyl]benzoic acid (14.28 g), 4-dimethylaminopyridine (4.39 g), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (8.34 g) and 2-methylbenzenesulfonamide (5.85 g) was dissolved in dry methylene chloride (270 mL) and the solution was stirred under an inert atmosphere for 48 h. The mixture was diluted with methylene chloride (300 mL) and washed three times with 1N hydrochloric acid. The combined hydrochloric washes were back washed with methylene chloride. The combined organic extracts were washed twice with water and evaporated. The residue was dissolved in a small volume of methanol and 1N sodium hydroxide and this solution was purified by flash chromatography over octadecylsilyl bonded silica gel ("Regis PREP-40-ODS" -irregularly shaped 32-74μ diameter particles, 72% silanol coverage, 21% carbon load) (450 g) eluting with 50:50 methanol:water, pH 7.1. The appropriate fractions (TLC, Rf =0.73, octadecylisilyl bonded silica gel, 200μ layer, 12% carbon load, 80:20 methanol:water, pH 6.1, 0.1% ammonium acetate buffer) were combined, the methanol evaporated, and the residual aqueous solution acidified to pH 1 with 1N hydrochloric acid. The resultant precipitate was filtered, washed (water), and dried under vacuum to give the title compound (16.7 g, 88%) as a white solid; mp 117°-120° C.; ee at least 99%.

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