Dichloromethane → (3R,4R,5S,6R)-3-amino-6-(hydroxymethyl)oxane-2,4,5-triol hydrochloride

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Reaction Steps

Compound [16] (0.34-6.88 g, 0.9-18 mmol) is dissolved in anhydrous methanol (5-180 ml), and catalytic amounts of sodium methylate (prepared from 0.005-0.09 g of sodium in 0.2-2.9 ml of methanol) are added. After the reaction is complete, the mixture is neutralized with an acidic ion exchanger (0.3-6.7 g Amerlite IR-120, H+ -form) and evaporated. The resulting reaction product is taken up in anhydrous dimethylformamide (5-140 ml) and sodium hydride (0.16-3.21 g, 6.75-135 mmol) and benzyl bromide (0.92-18.46 g, 5.4-108 mmol) are added. After the reaction is complete, methanol (0.16-3.2 g, 5-100 mmol) is added, and the mixture is diluted with ethyl acetate and washed successively with saturated ammonium chloride and saturated sodium bicarbonate solutions. The crude product after chromatography on silica gel (ethyl acetate/isohexane gradient) is subsequently taken up in dry dichloromethane (8-120 mol) and, at -78° C., dimethylaminosulfur trifluoride (0.36-7.09 g, 2.69-53.18 mmol) and N-bromosuccinimide (0.16-4.73 g, 1.35-26.6 mmol) are added, and the mixture is warmed to room temperature. After washing with saturated sodium bicarbonate solution, the mixture is concentrated, and the byproducts of the reaction are removed by silica gel chromatography (stepwise gradient: ethyl acetate/isohexane) to result in compound [1] (0.33-6.47 g, 0.72-14.4 mmol, about 80% yield). FAB-MS: M+H+ =450. NMR data consistent with Nicolaou et al., J. Am. Chem. Soc. 114:3127 (1992) and C. W. Hummel, Ph.D. Dissertation, The University of California, San Diego (1993).

Provenance & Evidence