Dimethylformamide → N-(4-(4-amino-2-fluorophenoxy)pyridin-2-yl)morpholine-4-carboxamide

HRID 492761Notes

Reaction equation

HRID 492761 reaction equation
[F: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+].CN(C)C=O>C(O)C.[Fe].O.C(OCC)(=O)C>[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[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)=[O:13])[CH:6]=2)=[C:2]([F:1])[CH:23]=1

Participants

8

Reactant 3

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 57677388N-[4-(2-fluoro-4-nitrophenoxy)pyridin-2-yl]morpholine-4-carboxamide

Product 1

HCID 57677752N-(4-(4-amino-2-fluorophenoxy)pyridin-2-yl)morpholine-4-carboxamideYield 87.9%

Reagents, catalysts & solvents 4

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of morpholine-4-carboxylic acid [4-(2-fluoro-4-nitrophenoxy)pyridin-2-yl]amide (941 mg) in ethanol (50 ml) were added water (10 ml), electrolytic iron powder (581 mg), ammonium chloride (1.11 g) and N,N-dimethylformamide (0.75 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 washed with water and N,N-dimethylformamide in this order. The filtrate was concentrated under a reduced pressure to give a residue, to which ethyl acetate (100 ml) and water (100 ml) were added to partition. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; hexane:ethyl acetate=1:1 to 1:2, ethyl acetate, then ethyl acetate:methanol=20:1 to 10:1). Fractions containing the target compound were concentrated to provide the titled compound (759 mg, 87.8%) as a pale yellow oil.

Workup

  1. temperatureThe reaction mixture was cooled down to room temperature
  2. filtrationfiltered
  3. customto remove an insoluble portion, which
  4. washwas washed with water and N,N-dimethylformamide in this order
  5. concentrationThe filtrate was concentrated under a reduced pressure
  6. customto give a residue
  7. customto partition
  8. extractionThe aqueous layer was extracted with ethyl acetate
  9. washThe combined organic layer was washed with water and brine in this order
  10. dry with materialdried over anhydrous sodium sulfate
  11. customThe solvent was evaporated under a reduced pressure
  12. customto give a residue, which
  13. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent
  14. additionFractions containing the target compound
  15. concentrationwere concentrated

Sources & evidence

ORD record
ord-c0b08ddcccc8474eb500e72b20d583b8
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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