p-Fluoronitrobenzene → 4-(4-Nitrophenyl)-morpholin-3-ON

HRID 730162Notes

Reaction equation

HRID 730162 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-:21])=[O:20])=[CH:15][CH:14]=1>CN1CCCC1=O>[N:3]1([C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[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 114473754-(4-Nitrophenyl)-morpholin-3-ON

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 1). 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 1 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 1 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-a8309f7ff4bd4d458747a481044f05d3
Source dataset
uspto-grants-2009_09
Patent number
US07582666B2

Reaction notes

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