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

Temperature

46 °C

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%).

1. filtrationThe precipitate was filtered off
2. concentrationthe mixture was concentrated
3. custompurified by flash chromatography on silica gel
4. dissolutionThe purified product of 4-O-benzyl-2-deoxy-2-C-hydroxymethyl-D-xylo-pentodialdose was dissolved in methanol (50 ml)
5. stirringThe mixture was stirred at room temperature for 3 days
6. customevaporated to dryness
7. dissolutionThe residue was dissolved in water (50 ml)
8. extractionthe solution was extracted with methylene chloride
9. dry with materialThe organic phase was dried over magnesium sulphate
10. customevaporated
11. custompurified on silica gel

ORD record

ord-28d58b4099434502bc3fc034b5f2b703

Source dataset

uspto-grants-2000_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06046214