Water → 3-((2-Chloropyridin-4-yl)oxy)-2-methyl-6-nitropyridine

HRID 626498Notes

Reaction equation

HRID 626498 reaction equation
Br[C:2]1[C:3]([CH3:11])=[N:4][C:5]([N+:8]([O-:10])=[O:9])=[CH:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].[Cl:18][C:19]1[CH:24]=[C:23]([OH:25])[CH:22]=[CH:21][N:20]=1.O>CN(C=O)C.CCOC(C)=O>[Cl:18][C:19]1[CH:24]=[C:23]([O:25][C:2]2[C:3]([CH3:11])=[N:4][C:5]([N+:8]([O-:10])=[O:9])=[CH:6][CH:7]=2)[CH:22]=[CH:21][N:20]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 674264093-Bromo-2-methyl-6-nitropyridineHCID 178516507HCID 178516507, compound

Product 1

HCID 904036213-((2-Chloropyridin-4-yl)oxy)-2-methyl-6-nitropyridineYield 55%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 3-bromo-2-methyl-6-nitropyridine (25.59 g, 118 mmol), K2CO3 (48.9 g, 354 mmol) and 2-chloro-4-hydroxy-pyridine (30.6 g, 236 mmol) in DMF (160 mL) was sparged with Ar, heated at 100° C. overnight, then cooled to RT. The mixture was treated with water and EtOAc, the solids removed via filtration through diatomaceous earth and washed with water, EtOAc, then DCM. The aqueous filtrate was extracted with EtOAc (2×) and the organic extracts were combined with the organic filtrates, washed with water, then brine, dried over Na2SO4 and concentrated to dryness. The residue was treated with MTBE, sonicated and the resulting solid collected via filtration to afford 3-((2-chloropyridin-4-yl)oxy)-2-methyl-6-nitropyridine (17.16 g, 55%). 1H NMR (400 MHz, DMSO-d6): δ 8.38 (d, J=5.7 Hz, 1H), 8.25 (d, J=8.7 Hz, 1H), 7.95 (d, J=8.7 Hz, 1H), 7.29 (d, J=2.3 Hz, 1H), 7.16 (dd, J=5.7, 2.3 Hz, 1H), 2.46 (s, 3H); MS (ESI) m/z: 266.0 (M+H+).

Workup

  1. temperaturecooled to RT
  2. customthe solids removed via filtration through diatomaceous earth
  3. washwashed with water, EtOAc
  4. extractionThe aqueous filtrate was extracted with EtOAc (2×)
  5. washwashed with water
  6. dry with materialbrine, dried over Na2SO4
  7. concentrationconcentrated to dryness
  8. additionThe residue was treated with MTBE
  9. customsonicated
  10. filtrationthe resulting solid collected via filtration

Sources & evidence

ORD record
ord-f02e32c57d764a2fbea38053d6775503
Source dataset
uspto-grants-2016_04
Patent number
US09309224B2

Reaction notes

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