tert-Butyl methyl ether → 1-(6-Amino-5-nitro-2-pyridyl)-2-(2,4-difluorophenyl)ethane-1,2-dione

HRID 2065783Notes

Reaction equation

HRID 2065783 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.[Mn]([O-])(=O)(=O)=[O:22].[K+].S([O-])([O-])(=O)=S.[Na+].[Na+].C(OC)(C)(C)C.[Cl-].[Na+].[OH2:42]>CC(C)=O.C(OCC)(=O)C>[NH2:17][C:15]1[N:16]=[C:11]([C:10](=[O:22])[C:9]([C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])=[O:42])[CH:12]=[CH:13][C:14]=1[N+:18]([O-:20])=[O:19]

Participants

8

Reactant 5

HCID 15413tert-Butyl methyl etherHCID 24477Sodium ThiosulfateHCID 516875Potassium PermanganateHCID 57417360Sodium chloride; waterHCID 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-dione

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
15 °C

Procedure

To a cold suspension (0-10° C.) of 6-[2-(2,4-difluorophenyl)ethynyl]-3-nitro-pyridin-2-amine (500 g, 1.82 mol) in acetone (10 L), is added cold buffer [NaH2PO4 (0.8 M)/Na2HPO4 (0.8 M)=85/15 (V/V)] (pH=6.0; 0-10° C.; 10 L). The temperature is maintained at 15° C. Potassium permanganate (1035 g, 6.55 mol) is added portionwise (3 portions). The mixture is stirred for 4 h at 15° C. The pH is adjusted to pH=5.0 and the temperature is kept below 15° C. A 28% sodium thiosulfate solution (2054 mL, 3.64 mol) is added slowly, maintaining the temperature below 15° C. and the pH below 7.5. Brine (7.5 L) and a mixture of methyl tert-butyl ether (3.75 L) and ethyl acetate (3.75 L) are added to the suspension. The mixture is stirred for 15 min at 13° C. The two phases are separated and the aqueous brown suspension is extracted twice with methyl tert-butyl ether (3.5 L). The combined organic layers are collected and washed with brine (2×3 L), dried over Na2SO4, filtered, and the solvent is evaporated under reduced pressure to obtain the title compound as a yellow solid (375 g). The experiment is repeated under the same conditions twice more. The resulting batches are combined to afford 1080 g. LC-ES/MS m/z 308 (M+1).

Workup

  1. customis kept below 15° C
  2. temperaturemaintaining the temperature below 15° C.
  3. additionare added to the suspension
  4. stirringThe mixture is stirred for 15 min at 13° C
  5. customThe two phases are separated
  6. extractionthe aqueous brown suspension is extracted twice with methyl tert-butyl ether (3.5 L)
  7. customThe combined organic layers are collected
  8. washwashed with brine (2×3 L)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. customthe solvent is evaporated under reduced pressure

Sources & evidence

ORD record
ord-5d3b5685f6444af6a7f806a8d4bf1b70
Source dataset
uspto-grants-2012_10
Patent number
US08288548B2

Reaction notes

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