Trimethylsilyl triflate → HCID 67292619, compound

HRID 46204Notes

Reaction equation

HRID 46204 reaction equation
[Cl:1][C:2]1[CH:22]=[CH:21][C:20]([C@H:23]2[C@H:28]([O:29]CC3C=CC=CC=3)[C@@H:27]([O:37]CC3C=CC=CC=3)[C@H:26]([O:45]CC3C=CC=CC=3)[C@@H:25]([CH2:53][O:54]CC3C=CC=CC=3)[O:24]2)=[CH:19][C:3]=1[CH2:4][C:5]1[N:6]=[N:7][C:8]([C:11]#[C:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:9][CH:10]=1.FC(F)(F)S(O[Si](C)(C)C)(=O)=O.C[O-].[Na+].[H][H]>C(OC(=O)C)(=O)C.CO>[Cl:1][C:2]1[CH:22]=[CH:21][C:20]([CH:23]2[CH:28]([OH:29])[CH:27]([OH:37])[CH:26]([OH:45])[CH:25]([CH2:53][OH:54])[O:24]2)=[CH:19][C:3]=1[CH2:4][C:5]1[N:6]=[N:7][C:8]([C:11]#[C:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:9][CH:10]=1

Participants

7

Reactant 4

HCID 65367Trimethylsilyl triflateHCID 10942334Sodium MethoxideHCID 672875763-(2-Chloro-5-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-tetrahydro-2H-pyran-2-yl)benzyl)-6-(phenylethynyl)pyridazineHCID 178418361HCID 178418361, compound

Product 1

HCID 67292619HCID 67292619, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 7918Acetic AnhydrideSolvent2×

Procedure

To a solution of 3-(2-chloro-5-((2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-(benzyloxymethyl)-tetrahydro-2H-pyran-2-yl)benzyl)-6-(phenylethynyl)pyridazine (0.5 mmol) from step 1 at −30° C. in acetic anhydride (10 mL) was slowly added a solution of trimethylsilyl trifluoromethanesulfonate (0.73 mL, 4.0 mmol) in acetic anhydride (5 mL). The resulting mixture was stirred with gradual warming to ambient temperature over 15 h, cooled to 0° C., and quenched with saturated sodium bicarbonate. After dilution with ethyl acetate, the organic layer was washed with sodium bicarbonate and brine prior to drying over magnesium sulfate. Filtration and removal of volatiles under reduced pressure yielded peracetylated compound as a brown amorphous solid. Deacetylation was achieved by addition of sodium methoxide (25 wt % in methanol, 1 mL) to a solution of this residue in methanol (10 mL). The reaction mixture was stirred at ambient temperature for 2 h. Amberlite® IR120 hydrogen form was then added to neutralize the reaction mixture. The resin was filtered off and the filtrate was concentrated in vacuo. Purification by reverse phase preparative HPLC (Gilson®, SunFire™ Prep, 5 to 50% acetonitrile in water gradient) provided the title compound (41 mg, 0.10 mmol, 25%) as a white solid.

Workup

  1. temperaturecooled to 0° C.
  2. customquenched with saturated sodium bicarbonate
  3. washAfter dilution with ethyl acetate, the organic layer was washed with sodium bicarbonate and brine
  4. dry with materialto drying over magnesium sulfate
  5. filtrationFiltration and removal of volatiles under reduced pressure
  6. customyielded peracetylated compound as a brown amorphous solid
  7. stirringThe reaction mixture was stirred at ambient temperature for 2 h
  8. filtrationThe resin was filtered off
  9. concentrationthe filtrate was concentrated in vacuo
  10. customPurification by reverse phase preparative HPLC (Gilson®, SunFire™ Prep, 5 to 50% acetonitrile in water gradient)

Sources & evidence

ORD record
ord-97602a4692eb493c9dffe6d172c22b07
Source dataset
uspto-grants-2013_09
Patent number
US08541380B2

Reaction notes

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