Sodium borohydride → tert-butyl (2S,3S)-4-chloro-1-cyclohexyl-3-hydroxybutan-2-ylcarbamate

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Reaction Steps

To a solution of the crude (S)-tert-butyl 4-chloro-1-cyclohexyl-3-oxobutan-2-ylcarbamate (5.8 g, 0.019 mol) in 9:1 THF/H2O (100 mL) at 0° C. was added NaBH4 (1.8 g, 0.047 mmol). After stirring for 45 min at rt, the solvent was removed in vacuo. The residue was diluted with water (50 mL) and the aqueous layer was extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated to give the crude product which was purified by flash chromatography to give a mixture of isomeric alcohols, which was recrystallized from n-hexane three times to give pure tert-butyl (2S,3S)-4-chloro-1-cyclohexyl-3-hydroxybutan-2-ylcarbamate (1.15 g, 40%). 1H NMR: 0.82 (m, 1H), 0.96 (m, 1H), 1.08-1.40 (m, 5H), 1.43 (s, 9H), 1.65 (m, 4H), 1.82 (m, 1H), 3.08 (m, 1H), 3.52 (m, 1H), 3.58 (r, 1H), 3.79 (m, 2H), 4.51 (m, 1H). MS (E/Z): 306 (M+H+). The mother liquor was concentrated and recrystallized from n-hexane three times to give pure tert-butyl (2S,3R)-4-chloro-1-cyclohexyl-3-hydroxybutan-2-ylcarbamate (0.3 g, 10.3%).

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