Water → 3-Amino-6-(3-methoxy-4-methylphenoxy)pyridine

HRID 1023541Notes

Reaction equation

HRID 1023541 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][N:10]=2)=[CH:4][C:3]=1[O:18][CH3:19].O.[Cl-].[NH4+]>O1CCCC1.[Fe]>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[N:10]=[CH:11][C:12]([NH2:15])=[CH:13][CH:14]=2)=[CH:4][C:3]=1[O:18][CH3:19]

Participants

6

Reactant 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 672369462-(3-Methoxy-4-methylphenoxy)-5-nitropyridine2×

Product 1

HCID 672355973-Amino-6-(3-methoxy-4-methylphenoxy)pyridineYield 92.5%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-{[4-methyl-3-(methyloxy)phenyl]oxy}-5-nitropyridine (Intermediate 49, 568 mg) in tetrahydrofuran (25 mL)/water (12.50 mL), iron (609 mg, 10.91 mmol) and then ammonium chloride (584 mg, 10.91 mmol) were added and the reaction mixture was stirred for 8 hours at room temperature. The catalyst was filtered off and the solution was diluted with an aqueous saturated solution of Na2CO3 (5 mL) and extracted with ethyl acetate (2 times 40 mL). Combined organic layers were dried over sodium sulphate, filtered and evaporated and the residue was purified by silica gel chromatography (Biotage system with a 50 g SNAP column) using a as eluent a gradient cyclohexane/ethyl acetate from 8/2 to 1/1. Evaporation afforded the title compound as light yellow oil (465 mg).

Workup

  1. filtrationThe catalyst was filtered off
  2. additionthe solution was diluted with an aqueous saturated solution of Na2CO3 (5 mL)
  3. extractionextracted with ethyl acetate (2 times 40 mL)
  4. dry with materialCombined organic layers were dried over sodium sulphate
  5. filtrationfiltered
  6. customevaporated
  7. customthe residue was purified by silica gel chromatography (Biotage system with a 50 g SNAP column)
  8. customEvaporation

Sources & evidence

ORD record
ord-1fa22a35e00448aabfc8a13b35e82db3
Source dataset
uspto-grants-2014_05
Patent number
US08722695B2

Reaction notes

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