Sodium Sulfate → 2-(Difluoromethoxy)-5-nitropyridine

HRID 1875894Notes

Reaction equation

HRID 1875894 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.S([O-])([O-])(=O)=O.[Na+].[Na+].[F:18][C:19]([F:27])(S(F)(=O)=O)C(O)=O>C(#N)C>[F:18][CH:19]([F:27])[O:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 24436Sodium SulfateHCID 27375162,2-Difluoro-2-(fluorosulfonyl)acetic acidHCID 178526703HCID 178526703, compound

Product 1

HCID 534037522-(Difluoromethoxy)-5-nitropyridineYield 49.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To 2-hydroxy-5-nitropyridine (7 g, 50 mmol) in acetonitrile (500 mL) was added sodium sulfate (1.5 g, 10.6 mmol), and 2,2-difluoro-2-(fluorosulfonyl)acetic acid (6.2 mL, 60 mmol) and the reaction was allowed to stir at room temperature for 16 hours. The reaction was quenched with saturated aqueous sodium bicarbonate and the acetonitrile was removed in vacuo. The remaining aqueous component was extracted with ethyl acetate, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The pale brown oily solid was triturated with ether/hexanes, filtered and the filtrate concentrated to afford 2-(difluoromethoxy)-5-nitropyridine (4.7 g, 24.7 mmol, 49% yield) as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.14 (d, J=2.76 Hz, 1H), 8.68 (dd, J=9.03, 2.76 Hz, 1H), 7.98 (s, 0.5H), 7.62 (s, 0.5H), 7.34 (d, J=9.03 Hz, 1H).

Workup

  1. customThe reaction was quenched with saturated aqueous sodium bicarbonate
  2. customthe acetonitrile was removed in vacuo
  3. extractionThe remaining aqueous component was extracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe pale brown oily solid was triturated with ether/hexanes
  9. filtrationfiltered
  10. concentrationthe filtrate concentrated

Sources & evidence

ORD record
ord-46ab34806c384f4187f19d8f668fee81
Source dataset
uspto-grants-2012_11
Patent number
US08309577B2

Reaction notes

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