Ammonium Chloride → 4-[(6-Methylpyridin-3-yl)oxy]pyridin-3-amine

HRID 1642270Notes

Reaction equation

HRID 1642270 reaction equation
[Cl-].[NH4+].[CH3:3][C:4]1[N:9]=[CH:8][C:7]([O:10][C:11]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[N+:17]([O-])=O)=[CH:6][CH:5]=1>C(O)C.O.[Fe]>[CH3:3][C:4]1[N:9]=[CH:8][C:7]([O:10][C:11]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[NH2:17])=[CH:6][CH:5]=1

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 575503212-Methyl-5-[(3-nitropyridin-4-yl)oxy]pyridine

Product 1

HCID 575503144-[(6-Methylpyridin-3-yl)oxy]pyridin-3-amineYield 79%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a refluxing mixture of iron powder (2.55 g, 45.93 mmol) and ammonium chloride (307 mg, 5.74 mmol) in ethanol (45 mL) and water (8 mL) was added 4-(6-methyl-pyridin-3-yloxy)-3-nitropyridine (AMR01121, 1.93 g, 8.35 mmol) and the resulting mixture was stirred at reflux for 2 h. After removal of the solvent, the residue was diluted in aqueous sodium hydrogen carbonate (40 mL) and extracted with DCM (3×20 mL). The organic layer was dried (MgSO4), filtered and evaporated. Flash master chromatography of the crude product using DCM to DCM/MeOH 9:1 gradient as eluent gave 4-(6-methylpyridin-3-yloxy)-pyridin-3-ylamine (1.32 g, 79%) as an orange solid, mp 74-79° C.

Workup

  1. temperatureat reflux for 2 h
  2. customAfter removal of the solvent
  3. additionthe residue was diluted in aqueous sodium hydrogen carbonate (40 mL)
  4. extractionextracted with DCM (3×20 mL)
  5. dry with materialThe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-8d2d5ef517bb48d3a3614383fbe1bee6
Source dataset
uspto-grants-2012_02
Patent number
US08119627B2

Reaction notes

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