p-Fluoronitrobenzene → 4-(4-Aminophenyl)morpholin-3-one

HRID 1796940Notes

Reaction equation

HRID 1796940 reaction equation
[H-].[Na+].[NH:3]1[CH2:8][CH2:7][O:6][CH2:5][C:4]1=[O:9].[H][H].F[C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-])=O)=[CH:15][CH:14]=1>CN1CCCC1=O>[N:3]1([C:13]2[CH:18]=[CH:17][C:16]([NH2:19])=[CH:15][CH:14]=2)[CH2:8][CH2:7][O:6][CH2:5][C:4]1=[O:9]

Participants

6

Reactant 4

HCID 9590p-FluoronitrobenzeneHCID 24758Sodium hydrideHCID 669533-MorpholinoneHCID 178418361HCID 178418361, compound

Product 1

HCID 111948544-(4-Aminophenyl)morpholin-3-one

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Over a period of 2 hours, sodium hydride (88 g, 2.2 mol, 60% in paraffin) is added a little at a time to a solution of morpholin-3-one (202 g, 2 mol) in N-methylpyrrolidone (2 l). After the evolution of hydrogen has ceased, 4-fluoronitrobenzene (282 g, 2 mol) is added dropwise with cooling over a period of one hour, and the reaction mixture is stirred overnight. At 12 mbar and 76° C., 1.7 l of the volume of the liquid is then distilled off, the residue is poured into water (2 l) and this mixture is extracted twice with ethyl acetate (in each case 1 l). The combined organic phases are washed with water, dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification is carried out by chromatography (on silica gel, hexane/ethyl acetate 1:1) and subsequent crystallization from ethyl acetate. Yield: 78 g (colorless to brownish solid), 17.6% of theory.

Workup

  1. temperaturewith cooling over a period of one hour
  2. distillationAt 12 mbar and 76° C., 1.7 l of the volume of the liquid is then distilled off
  3. additionthe residue is poured into water (2 l)
  4. extractionthis mixture is extracted twice with ethyl acetate (in each case 1 l)
  5. washThe combined organic phases are washed with water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification
  10. customis carried out by chromatography (on silica gel, hexane/ethyl acetate 1:1) and subsequent crystallization from ethyl acetate

Sources & evidence

ORD record
ord-39b632dafd7146d58e86bee148f56c58
Source dataset
uspto-grants-2006_04
Patent number
US07034017B2

Reaction notes

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