Hydrochloric Acid → (3R,4R,5R)-1-benzyl-3-benzyloxy-5-hydroxymethylpiperidin-4-ol

Participants

Reaction Conditions

Reaction Steps

4-O-Benzyl-2-deoxy-2-C-hydroxymethyl-D-glucopyranose (6.0 g, 21.1 mmol) (preparation see WO 95/24391) was dissolved in methanol (200 ml). Sodium periodate (21.4 g, 100 mmol) in water (200 ml) was added dropwise over 15 min. The mixture was stirred at 45-47° C. for 3.5 h. The precipitate was filtered off and the mixture was concentrated and purified by flash chromatography on silica gel using ethyl acetate as eluent. The purified product of 4-O-benzyl-2-deoxy-2-C-hydroxymethyl-D-xylo-pentodialdose was dissolved in methanol (50 ml) and benzyl amine (4.36 g, 40.7 mmol) and sodium cyanoborohydride (1.0 g, 15.9 mmol) was added. The mixture was stirred at room temperature for 3 days. Subsequently the mixture was acidified to pH=2 with conc. hydrochloric acid and evaporated to dryness. The residue was dissolved in water (50 ml), pH was adjusted to 10 with aqueous sodium hydroxide and the solution was extracted with methylene chloride. The organic phase was dried over magnesium sulphate, evaporated and purified on silica gel using ethyl acetate as eluent. This afforded (3R,4R,5R)-1-benzyl-3-benzyloxy-5-hydroxymethylpiperidin-4-ol as an oil (Yield: 25%).

Provenance & Evidence