Benzyl Alcohol → benzyl 2-acetamido-2-deoxy-6-(dimethyl-phosphinyl)-a-D-mannopyranoside

HRID 564896Notes

Reaction equation

HRID 564896 reaction equation
[OH:1][CH:2]1[O:9][C@H:8]([CH2:10][OH:11])[C@@H:6]([OH:7])[C@H:4]([OH:5])[C@@H:3]1[NH:12][C:13]([CH3:15])=[O:14].CC(OC(C)=O)=O.[CH2:23](O)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.B(F)(F)F.CCOCC.[CH3:40][P:41](Cl)([CH3:43])=[O:42].C(N[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OCC1C=CC=CC=1)(=O)C.N1C(C)=CC=CC=1C>C[N+]([O-])=O.CN(C=O)C.N1C=CC=CC=1>[C:13]([NH:12][C@H:3]1[C@@H:4]([OH:5])[C@H:6]([OH:7])[C@@H:8]([CH:10]([P:41]([CH3:43])([CH3:40])=[O:42])[OH:11])[O:9][C@@H:2]1[O:1][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)(=[O:14])[CH3:15]

Participants

11

Reactant 7

HCID 244Benzyl AlcoholHCID 7918Acetic AnhydrideHCID 79372,6-LutidineHCID 8000Boron trifluoride etherateHCID 439281N-Acetyl-D-MannosamineHCID 517954Dimethylphosphinic chlorideHCID 11845169benzyl 2-acetamido-2-deoxy-a-D-mannopyranoside

Product 1

HCID 54159087benzyl 2-acetamido-2-deoxy-6-(dimethyl-phosphinyl)-a-D-mannopyranosideYield 56%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent2×HCID 6375NitromethaneSolvent

Procedure

A solution of ManNAc (5.0 g, 2.6 mmol), Ac2O (10 mL) and pyridine (20 mL) was stirred for 10 hours at room temperature, and the mixture was concentrated, followed by coevaporation with toluene. A solution of the residue, benzyl alcohol (20 mL), BF3.OEt2 (1.6 g, 11.3 mmol) in CH3NO2 (150 mL) was gently refluxed for 2.5 hours. After cooling, the mixture was concentrated. The residue was chromatographed on silica gel, with toluene-EtOAc (1:2). The isolated benzyl 2-acetamido-4,5,6-tri-O-acetyl-2-deoxy-a-D-mannopyranoside and 0.15 g of NaOMe was dissolved in MeOH (100 mL) and the solution was stirred for 30 minutes at room temperature, and neutralized by addition of Dowex 50W-X8 (H+). After the resin was filtered off, the filtrate was concentrated, followed by coevaporation with pyridine. A solution of dimethylphosphinic chloride (1 g, 8.8 mmol) in DMF was added to a cold solution of benzyl 2-acetamido-2-deoxy-a-D-mannopyranoside (0.50 g, 1.6 mmol), 2,6-lutidine (0.34 g, 3.2 mmol) in anhydrous DMF (30 mL) in a dry ice-acetone bath, and the reaction was allowed to slowly warm to room temperature. The reaction was monitered by TLC with (1M NH4OAc/2-proponal/EtOAc, 1/2.4/3.4). After 10 hours, the reaction mixture was directly applied to silica gel chromatography, eluted with CHCl3/EtOAc/MeOH (5/2/1) to give benzyl 2-acetamido-2-deoxy-6-(dimethyl-phosphinyl)-a-D-mannopyranoside (56 percent yield).

Workup

  1. concentrationthe mixture was concentrated
  2. temperatureAfter cooling
  3. concentrationthe mixture was concentrated
  4. customThe residue was chromatographed on silica gel, with toluene-EtOAc (1:2)
  5. dissolutionThe isolated benzyl 2-acetamido-4,5,6-tri-O-acetyl-2-deoxy-a-D-mannopyranoside and 0.15 g of NaOMe was dissolved in MeOH (100 mL)
  6. additionneutralized by addition of Dowex 50W-X8 (H+)
  7. filtrationAfter the resin was filtered off
  8. concentrationthe filtrate was concentrated
  9. temperatureto slowly warm to room temperature
  10. waitAfter 10 hours
  11. washeluted with CHCl3/EtOAc/MeOH (5/2/1)

Sources & evidence

ORD record
ord-981381a3861a4087a1426818305a35c7
Source dataset
uspto-grants-2001_01
Patent number
US06168934A

Reaction notes

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