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

HRID 492689Notes

Reaction equation

HRID 492689 reaction equation
[CH3:1][C:2]1[CH:23]=[C:22]([N+:24]([O-])=O)[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:12]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[O:13])[CH:6]=1.[Cl-].[NH4+].O>C(O)C.C(OCC)(=O)C.C(OCC)C.[Fe]>[NH2:24][C:22]1[CH:21]=[CH:20][C:3]([O:4][C:5]2[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)=[O:13])[CH:6]=2)=[C:2]([CH3:1])[CH:23]=1

Participants

8

Reactant 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 57677327N-[4-(2-Methyl-4-nitrophenoxy)-2-pyridinyl]-4-morpholinecarboxamide

Product 1

HCID 57677565Morpholine-4-carboxylic acid [4-(4-amino-2-methylphenoxy)pyridin-2-yl]amideYield 26.1%

Reagents, catalysts & solvents 4

HCID 23925IronCatalystHCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of morpholine-4-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 20 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 then partitioned between ethyl acetate:tetrahydrofuran=1:1 (200 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, which was then suspended in ethyl acetate (5 ml), and diluted with diethyl ether (30 ml). The solid was filtered, and dried under aeration to provide the titled compound (184 mg, 26.1%) as colorless powder. The mother liquor was concentrated to give a residue, which was suspended in diethyl ether (30 ml). The solid was filtered, and dried under aeration to further provide the titled compound (207 mg, 29.3%) as pale yellow 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 then partitioned between ethyl acetate
  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, which
  12. filtrationThe solid was filtered
  13. customdried under aeration

Sources & evidence

ORD record
ord-dba73ec35ebe4f668dafec787244909d
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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