Sodium Phosphate, Dibasic → 1-(6-Amino-5-nitro-2-pyridyl)-2-(2,4-difluorophenyl)ethane-1,2-dione

HRID 2065799Notes

Reaction equation

HRID 2065799 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]#[C:10][C:11]1[N:16]=[C:15]([NH2:17])[C:14]([N+:18]([O-:20])=[O:19])=[CH:13][CH:12]=1.P([O-])(O)(O)=O.[Na+].P([O-])([O-])(O)=O.[Na+].[Na+].[Mn]([O-])(=O)(=O)=O.[K+].[OH2:40].[OH2:41].O.O.O.S([O-])([O-])(=O)=S.[Na+].[Na+]>O.CC(C)=O>[NH2:17][C:15]1[N:16]=[C:11]([C:10](=[O:41])[C:9]([C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])=[O:40])[CH:12]=[CH:13][C:14]=1[N+:18]([O-:20])=[O:19]

Participants

8

Reactant 5

HCID 24203Sodium Phosphate, DibasicHCID 61475Sodium Thiosulfate PentahydrateHCID 516875Potassium PermanganateHCID 23672064Monosodium phosphateHCID 677768706-[2-(2,4-Difluorophenyl)ethynyl]-3-nitro-pyridin-2-amine

Product 1

HCID 677771011-(6-Amino-5-nitro-2-pyridyl)-2-(2,4-difluorophenyl)ethane-1,2-dioneYield 75.8%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent3×

Conditions

Temperature
5 °C

Procedure

6-[2-(2,4-Difluorophenyl)ethynyl]-3-nitro-pyridin-2-amine (2.0 kg, 7.3 mol) and acetone (40.5 L) are added to a reactor under a nitrogen atmosphere and the mixture is cooled to 0-10° C. with stirring. A buffering solution of water (38.3 L), sodium dihydrogen phosphate (3.3 kg), and disodium hydrogen phosphate (0.7 kg) is added at 0-15° C. The mixture is cooled to 3-6° C. and is charged with solid potassium permanganate (4.1 kg, 25.9 mol) at 3-6° C. The mixture is stirred for 3 h to 5 h, and then portions of the reaction mixture are transferred to a vessel containing water (9.3 L) and sodium thiosulfate pentahydrate (3.6 kg) at 15-20° C. The mixture is stirred at 15-25° C. Water (50 L) is added and the mixture stirred for 0.5-1 h and is filtered. The filtrate is concentrated under reduced pressure below 45° C. When the distillation of solvent is complete, water (40 L) is added at 20-25° C. and the mixture is stirred for 0.5-1 h. The solids are collected by filtration and the filtercake is dried below 40° C. to obtain the title compound as a yellow solid (1.7 kg, 75%).

Workup

  1. temperatureThe mixture is cooled to 3-6° C.
  2. stirringThe mixture is stirred for 3 h to 5 h
  3. customportions of the reaction mixture are transferred to a vessel
  4. stirringThe mixture is stirred at 15-25° C
  5. stirringthe mixture stirred for 0.5-1 h
  6. filtrationis filtered
  7. concentrationThe filtrate is concentrated under reduced pressure below 45° C
  8. distillationWhen the distillation of solvent
  9. additionwater (40 L) is added at 20-25° C.
  10. stirringthe mixture is stirred for 0.5-1 h
  11. filtrationThe solids are collected by filtration
  12. customthe filtercake is dried below 40° C.

Sources & evidence

ORD record
ord-72bb4bb660404714a3825aea7936f443
Source dataset
uspto-grants-2012_10
Patent number
US08288548B2

Reaction notes

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