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

HRID 1637130Notes

Reaction equation

HRID 1637130 reaction equation
S1C=CC=C1[C@@:6]1(O[C@@H](C)[C@@H:18]([O:19]C(=O)C)[C@@H:13]([O:14]C(=O)C)[C@@H:8]1[O:9][C:10](=[O:12])[CH3:11])[OH:7].C[O-].[Na+].[H-].[Na+].[CH2:31](Br)[C:32]1[CH:37]=C[CH:35]=[CH:34][CH:33]=1.[Cl:39]CCl.C[N:43](S(F)(F)F)[CH3:44].BrN1C(=O)CCC1=O>CO.CN(C)C=O.C(OCC)(=O)C>[C:10]([O:9][CH2:8][CH3:6])(=[O:12])[CH3:11].[CH3:35][CH2:34][CH2:33][CH:32]([CH3:37])[CH3:31].[ClH:39].[OH:12][CH:10]1[O:9][C@H:8]([CH2:6][OH:7])[C@@H:13]([OH:14])[C@H:18]([OH:19])[C@H:44]1[NH2:43]

Participants

12

Reactant 7

HCID 6344DichloromethaneHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 67184N-bromobutanimideHCID 123203Sulfur, trifluoro(N-methylmethanaminato)-HCID 10942334Sodium MethoxideHCID 86755242HCID 86755242, compound

Product 2

HCID 2723635(3R,4R,5S,6R)-3-amino-6-(hydroxymethyl)oxane-2,4,5-triol hydrochlorideYield 80%HCID 21882781Isohexane ethyl acetate

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  1. customevaporated
  2. customThe resulting reaction product
  3. washwashed successively with saturated ammonium chloride and saturated sodium bicarbonate solutions
  4. washAfter washing with saturated sodium bicarbonate solution
  5. concentrationthe mixture is concentrated
  6. customthe byproducts of the reaction are removed by silica gel chromatography (stepwise gradient

Sources & evidence

ORD record
ord-4a9c811839aa457da80108a429c05e09
Source dataset
uspto-grants-2000_03
Patent number
US06037467

Reaction notes

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