Acetic Acid → 4-[3-((R)-2-Hydroxymethyl-pyrrolidin-1-yl)-propyl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester

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Reaction Steps

Sodium metaperiodate (505 mg, 2.36 mmol) and osmium(VIII) oxide (2.5% solution in tert-butylalcohol, 80 μl, 7.9 μmol) were added at 0° C. to a solution of 4-but-3-enyl-3-oxo-piperazine-1-carboxylic acid tert-butyl ester (200 mg, 0.79 mmol) in acetone/water 1:1 (10 ml). After 30 min, the reaction mixture was allowed to reach room temperature over 45 min, then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried (MgSO4), and evaporated. The crude aldehyde intermediate (3-oxo-4-(3-oxo-propyl)-piperazine-1-carboxylic acid tert-butyl ester) and D-prolinol (95 mg, 0.94 mmol) were dissolved in 1,2-dichloroethane (2 ml), then a freshly prepared solution of pyridine borane complex (8 M in pyridine, 0.24 ml, 1.9 mmol) and acetic acid (170 mg, 2.83 mmol) in ethanol (2 ml) was added dropwise at room temperature. The reaction mixture was stirred overnight, then 25%. aq. ammonium hydroxide solution (0.39 ml) was added, and volatile material was removed by rotary evaporation. The residue was purified by chromatography (SiO2; CH2Cl2/MeOH/NH4OH 80:20:0.25) to afford the title compound (160 mg, 60%). Light brown oil, MS (ISP) −342.1 (M+H)+.

Provenance & Evidence