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

HRID 1898310Notes

Reaction equation

HRID 1898310 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.Cl[C:12]([F:17])([F:16])C([O-])=O.[Na+]>C(#N)C>[F:16][CH:12]([F:17])[O:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 2734985Sodium chlorodifluoroacetateHCID 178526703HCID 178526703, compound

Product 1

HCID 534037522-(Difluoromethoxy)-5-nitropyridineYield 6.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-hydroxy-5-nitro pyridine (10 g, 0.071 mol) in acetonitrile (100 mL) was added sodium chlorodifluoroacetate (11.5 g, 0.075 mol). The reaction mass was refluxed for 72 h. The excess of solvent was removed under vacuum and the reaction mass was diluted with ethyl acetate and water. The organic layer was separated, dried over anhydrous sodium sulphate and concentrated. The obtained crude was purified by column chromatography on neutral alumina eluting with 10% EtOAc: Pet.ether to afford 0.900 g of the desired product. 1HNMR (DMSO-d6): δ 7.05 (d, J=8.7 Hz, 1H), 7.53 (d, J=71.4 Hz, 1H), 8.54 (dd, J=8.1 Hz & 5.4 Hz, 1H), 7.91 (s, 1H); MS [M]−: 190.83.

Workup

  1. temperatureThe reaction mass was refluxed for 72 h
  2. customThe excess of solvent was removed under vacuum
  3. additionthe reaction mass was diluted with ethyl acetate and water
  4. customThe organic layer was separated
  5. dry with materialdried over anhydrous sodium sulphate
  6. concentrationconcentrated
  7. customThe obtained crude
  8. customwas purified by column chromatography on neutral alumina eluting with 10% EtOAc

Sources & evidence

ORD record
ord-afe0624fb48e40d8a6ec645f950a9195
Source dataset
uspto-grants-2013_08
Patent number
US08519149B2

Reaction notes

Loading…