Morpholine → N-[4-(2-fluoro-4-nitrophenoxy)pyridin-2-yl]morpholine-4-carboxamide

HRID 492760Notes

Reaction equation

HRID 492760 reaction equation
[F:1][C:2]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH2:11])[CH:6]=1.C(N(CC)CC)C.Cl[C:27](OC1C=CC=CC=1)=[O:28].[NH:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1>O1CCCC1.C(OCC)C.CN(C)C=O>[F:1][C:2]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH:11][C:27]([N:36]2[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)=[O:28])[CH:6]=1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 231531982-Amino-4-(2-fluoro-4-nitrophenoxy)pyridine

Product 1

HCID 57677388N-[4-(2-fluoro-4-nitrophenoxy)pyridin-2-yl]morpholine-4-carboxamideYield 64.8%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(2-fluoro-4-nitrophenoxy)pyridin-2-ylamine (1.00 g) in tetrahydrofuran (50 ml) were added triethylamine (1.12 ml) and phenyl chloroformate (0.906 ml) while stirring in an ice bath, followed by stirring in an ice bath for 1 hr. The reaction mixture was concentrated under a reduced pressure to give a residue, to which N,N-dimethylformamide (16 ml) and morpholine (1.4 ml) were added, followed by stirring at room temperature for 4.5 hrs. The reaction mixture was partitioned between ethyl acetate (150 ml) and water (100 ml). The organic layer was washed with a 1 N aqueous solution of sodium hydroxide, brine, 1 N HCl and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to give a solid, which was then suspended in diethyl ether (50 ml), filtered, and dried under aeration to provide the titled compound (941 mg, 64.8%) as pale yellow powder.

Workup

  1. stirringby stirring in an ice bath for 1 hr
  2. concentrationThe reaction mixture was concentrated under a reduced pressure
  3. customto give a residue
  4. stirringby stirring at room temperature for 4.5 hrs
  5. customThe reaction mixture was partitioned between ethyl acetate (150 ml) and water (100 ml)
  6. washThe organic layer was washed with a 1 N aqueous solution of sodium hydroxide, brine, 1 N HCl and brine in this order
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was evaporated under a reduced pressure
  9. customto give a solid, which
  10. filtrationfiltered
  11. customdried under aeration

Sources & evidence

ORD record
ord-be8ca12dfe84479bb91fb0452db6a770
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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