Pyridine → HCID 11049983, compound

HRID 660002Notes

Reaction equation

HRID 660002 reaction equation
[CH2:1]([O:8][C@@H:9]1[C:13]([CH2:20][O:21][S:22]([CH3:25])(=[O:24])=[O:23])([CH2:14][O:15][S:16]([CH3:19])(=[O:18])=[O:17])[O:12][C@@H:11]([N:26]2[CH:34]=[C:32]([CH3:33])[C:30](=[O:31])[NH:29][C:27]2=[O:28])[C@H:10]1O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[N-:57]=[N+:58]=[N-:59].[Na+]>CN(C1C=CN=CC=1)C.CN(C=O)C.[Cl-].[Na+].O.ClCCl>[N:57]([C@@H:10]1[C@H:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:13]([CH2:20][O:21][S:22]([CH3:25])(=[O:24])=[O:23])([CH2:14][O:15][S:16]([CH3:19])(=[O:18])=[O:17])[O:12][C@H:11]1[N:26]1[CH:34]=[C:32]([CH3:33])[C:30](=[O:31])[NH:29][C:27]1=[O:28])=[N+:58]=[N-:59]

Participants

9

Reactant 4

HCID 1049PyridineHCID 33557Sodium AzideHCID 67749Trifluoromethanesulfonic anhydrideHCID 11827595HCID 11827595, compound

Product 1

HCID 11049983HCID 11049983, compoundYield 91.1%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of nucleoside 30 (5.35 g, 10 mmol) in anhyd dichloromethane (300 mL) was cooled to 0° C. Anhyd pyridine (8.08 mL, 100 mmol) and DMAP (4.89 g, 40 mmol) was added followed by the dropwise addition of trifluoromethansulfonic anhydride (3.3 mL, 20 mmol). After 2 h at 0° C. the reaction was quenched by the addition of ice cold sat. aq NaHCO3 (200 mL) and the reaction mixture was transferred to a separatory funnel. The phases were separated and the aq phase was extracted with dichloromethane (200 mL). The combined organic phases were washed with aq HCl (1.0 M, 2×300 mL) and sat. aq NaHCO3 (300 mL), dried (Na2SO4), filtered and concentrated in vacuo to give a white solid. The solid was dissolved in anhyd DMF (300 mL) and NaN3 (1.86 g, 30 mmol) was added. After stirring at rt for 4 h brine (300 mL) was added and the mixture was transferred to a separatory funnel. The aq phase was extracted with dichloromethane (3×200 mL) and the combined organic phases were dried (Na2SO4), filtered and concentrated in vacuo yielding a yellow residue that was purified by DCVC (Ø 5 cm, 25-100% EtOAc in n-heptane v/v, 5% increments, 100 mL fractions) affording nucleoside 32 (5.1 g, 91% from 30) as a white solid. Analytical data were identical to those reported above.

Workup

  1. customAfter 2 h at 0° C. the reaction was quenched by the addition of ice cold sat. aq NaHCO3 (200 mL)
  2. customthe reaction mixture was transferred to a separatory funnel
  3. customThe phases were separated
  4. extractionthe aq phase was extracted with dichloromethane (200 mL)
  5. washThe combined organic phases were washed with aq HCl (1.0 M, 2×300 mL) and sat. aq NaHCO3 (300 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a white solid
  10. additionwas added
  11. customthe mixture was transferred to a separatory funnel
  12. extractionThe aq phase was extracted with dichloromethane (3×200 mL)
  13. dry with materialthe combined organic phases were dried (Na2SO4)
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customyielding a yellow residue that
  17. customwas purified by DCVC (Ø 5 cm, 25-100% EtOAc in n-heptane v/v, 5% increments, 100 mL fractions)

Sources & evidence

ORD record
ord-3206b7ded1c54cbdb656875859a77a15
Source dataset
uspto-grants-2011_12
Patent number
US08084458B2

Reaction notes

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