Water → Pyrrolidine-1-carboxylic acid [4-(4-amino-2-methylphenoxy)pyridin-2-yl]amide

HRID 492691Notes

Reaction equation

HRID 492691 reaction equation
[CH3:1][C:2]1[CH:22]=[C:21]([N+:23]([O-])=O)[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:12]([N:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)=[O:13])[CH:6]=1.[Cl-].[NH4+].O.C(OCC)(=O)C>C(O)C.[Fe]>[NH2:23][C:21]1[CH:20]=[CH:19][C:3]([O:4][C:5]2[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:12]([N:14]3[CH2:18][CH2:17][CH2:16][CH2:15]3)=[O:13])[CH:6]=2)=[C:2]([CH3:1])[CH:22]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 57677612N-[4-(2-Methyl-4-nitrophenoxy)-2-pyridinyl]-1-pyrrolidinecarboxamide

Product 1

HCID 57677322Pyrrolidine-1-carboxylic acid [4-(4-amino-2-methylphenoxy)pyridin-2-yl]amideYield 66.2%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of pyrrolidine-1-carboxylic acid [4-(2-methyl-4-nitrophenoxy)pyridin-2-yl]amide (775 mg) in ethanol (50 ml) were added electrolytic iron powder (505 mg), ammonium chloride (967 mg) and water (10 ml), followed by stirring to heat at 90° C. for 30 min. The reaction mixture was cooled down to room temperature, and filtered to remove an insoluble portion, which was then washed with water and N,N-dimethylformamide in this order. The filtrate was concentrated under a reduced pressure to give a residue, which was partitioned between ethyl acetate (100 ml) and water (100 ml). The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, to which ethyl acetate (10 ml) was added, followed by allowing to stand at room temperature. After a solid precipitated, diethyl ether (30 ml) was added thereto, followed by stirring at room temperature for 2 hrs. The solid was filtered off, and dried under aeration to provide the titled compound (467 mg, 66.2%) as powder.

Workup

  1. temperatureThe reaction mixture was cooled down to room temperature
  2. filtrationfiltered
  3. customto remove an insoluble portion, which
  4. washwas then washed with water and N,N-dimethylformamide in this order
  5. concentrationThe filtrate was concentrated under a reduced pressure
  6. customto give a residue, which
  7. customwas partitioned between ethyl acetate (100 ml) and water (100 ml)
  8. washThe organic layer was washed with brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. customThe solvent was evaporated
  11. customto give a residue
  12. customto stand at room temperature
  13. customAfter a solid precipitated
  14. additiondiethyl ether (30 ml) was added
  15. stirringby stirring at room temperature for 2 hrs
  16. filtrationThe solid was filtered off
  17. customdried under aeration

Sources & evidence

ORD record
ord-2a5c242af70e4346868883b5aa10fa1d
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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