Sodium Hydroxide → (R)-4-(4-((2-(tert-butyldimethylsilyloxy)ethyl)(methyl)amino)-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide

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Reaction Steps

To a solution of (R)-4-(4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 45, 3.98 g, 8.25 mmol) and 2-(tert-butyldimethylsilyloxy)-N-methylethanamine (INTERMEDIATE 64, 1.56 g, 8.25 mmol) in 1,2-dichloroethane (27.5 ml) was added sodium triacetoxyborohydride (2.62 g, 12.37 mmol). The resulting mixture was stirred in the dark for 11.5 hours and then sodium hydroxide (0.5 M, aq., 50 ml) was added. The mixture was diluted with dichloromethane (70 ml) and stirred vigorously for 10 min. The layers were separated, and the organic layer was washed with saturated aqueous sodium bicarbonate. The organic layer was then diluted heavily with ethyl acetate and washed with saturated aqueous sodium chloride (×2) before being dried over sodium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (ISCO, 330 g SiO2, 0→50% ethyl acetate in hexanes over 30 min, then isocratic hold for 30 min, then 50→100% ethyl acetate in hexanes over 20 min) to afford the title product (2.68 g, yield: 49.5%). Additional impure title product was also obtained (1.65 g), which was further purified by reverse phase HPLC (Column: Xbridge Phenyl OBD 19 mm×100 mm, 5 μm; eluting with 65→80% acetonitrile in water (10 mM NH4OAc, pH 8) over 15 min). Product fractions were combined, diluted with saturated aqueous sodium bicarbonate, and extracted with ethyl acetate (×3). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford additional title product (1.05 g, yield: 19%).

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