1,4-Dioxane → 2-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-5-nitro-4-propan-2-yloxypyridine

HRID 518827Notes

Reaction equation

HRID 518827 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][CH:9]([CH3:11])[CH3:10])[C:5]([N+:12]([O-:14])=[O:13])=[CH:4][N:3]=1.O1[CH2:20][CH2:19]OCC1>>[CH3:4][N:3]1[CH2:20][CH:19]=[C:6]([C:2]2[CH:7]=[C:6]([O:8][CH:9]([CH3:11])[CH3:10])[C:5]([N+:12]([O-:14])=[O:13])=[CH:4][N:3]=2)[CH2:7][CH2:2]1

Participants

3

Reactant 2

HCID 312751,4-DioxaneHCID 866979922-Chloro-4-isopropoxy-5-nitropyridine

Product 1

HCID 866979932-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-5-nitro-4-propan-2-yloxypyridine

Conditions

Temperature
100 °C

Procedure

800 mg of 2-chloro-5-nitro-4-(propan-2-yloxy)pyridine are introduced into 62 ml of 1,4-dioxane. After sparging for 10 min with argon in the reaction mixture, 1.25 g of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine hydrochloride, 6.02 g of caesium carbonate, 6.2 ml of water and 467 mg of bis(triphenylphosphine)palladium(II) dichloride are added. The reaction mixture is heated at 100° C. for 16 h. After cooling, the mixture is run into water and extracted with ethyl acetate. The organic phase is washed with a saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification is carried out by flash chromatography on silica gel (40-63 microns), elution being carried out with a mixture of dichloromethane and methanol (90/10 to 80/20). 401 mg of 1′-methyl-5-nitro-4-(propan-2-yloxy)-1′,2′,3′,6′-tetrahydro-2,4′-bipyridine are obtained in the form of a yellow gum.

Workup

  1. customAfter sparging for 10 min with argon in the reaction mixture, 1.25 g of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine hydrochloride, 6.02 g of caesium carbonate, 6.2 ml of water and 467 mg of bis(triphenylphosphine)palladium(II) dichloride
  2. additionare added
  3. temperatureAfter cooling
  4. extractionextracted with ethyl acetate
  5. washThe organic phase is washed with a saturated sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification
  10. washis carried out by flash chromatography on silica gel (40-63 microns), elution
  11. additionbeing carried out with a mixture of dichloromethane and methanol (90/10 to 80/20)

Sources & evidence

ORD record
ord-3dbc21f41e9345e5adca7069c500584e
Source dataset
uspto-grants-2015_08
Patent number
US09115140B2

Reaction notes

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