Sodium borohydride → (3S)-3-(1-hydroxy-3-methyl-butyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

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Reaction Steps

Add sodium borohydride (15.2 g, 423 mmol) to a solution of (S)-3-(3-methylbutanoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (21.6 g, 84.6 mmol) in methanol (500 mL) portion wise and stir at room temperature overnight. Add another equivalent of sodium borohydride (3.04 g, 84.6 mmol). Stir for another 2 hours, evaporate the methanol to half the volume, add brine and extract with EtOAc. Dry the combined organic phases (MgSO4), filter and concentrate under reduced pressure. Separate the diastereoisomers by super critical fluid chromatography (AD-H column) eluting with 10% MeOH/CO2 with 0.2% diethylmethylamine to provide (3S)-3-(1-hydroxy-3-methyl-butyl)-pyrrolidine-1-carboxylic acid tert-butyl ester, isomer 1 (S-1) as the first eluting isomer (8.2 g, 38%) and (3S)-3-(1-hydroxy-3-methyl-butyl)-pyrrolidine-1-carboxylic acid tert-butyl ester, isomer 2 (S-2) as the second eluting isomer (8.9 g, 41%).

Provenance & Evidence