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

HRID 1091408Notes

Reaction equation

HRID 1091408 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][C:2]1=[O:7].[H-].[Na+].[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:1]1([C:13]2[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH:14]=2)[CH2:6][CH2:5][O:4][CH2:3][C:2]1=[O:7]

Participants

6

Reactant 4

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

Product 1

HCID 114473754-(4-Nitrophenyl)-morpholin-3-ONYield 17.6%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

2 mol (202 g) of morpholin-3-one (E. Pfeil, U. Harder, Angew. Chem. 79, 1967, 188) are dissolved in 21 of N-methylpyrrolidone (NMP). Over a period of 2 h, 88 g (2.2 mol) of sodium hydride (60% in paraffin) are then added a little at a time. After the evolution of hydrogen has ceased, 282 g (2 mol) of 4-fluoronitrobenzene are added dropwise with cooling at room temperature, over a period of 1 h, and the reaction mixture is then stirred overnight. At 12 mbar and 76° C., 1.7 l of the liquid volume are then distilled off, the residue is poured into 2 l of water and this mixture is extracted twice with in each case 1 l of ethyl acetate. After washing of the combined organic phases with water, the mixture is dried over sodium sulphate and the solvent is distilled off under reduced pressure. Purification is carried out by silica gel chromatography using hexane/ethyl acetate (1:1) and subsequent crystallization from ethyl acetate. This gives 78 g of product as a colourless to brownish solid, in a yield of 17.6% of theory.

Workup

  1. distillationAt 12 mbar and 76° C., 1.7 l of the liquid volume are then distilled off
  2. additionthe residue is poured into 2 l of water
  3. extractionthis mixture is extracted twice with in each case 1 l of ethyl acetate
  4. washAfter washing of the combined organic phases with water
  5. dry with materialthe mixture is dried over sodium sulphate
  6. distillationthe solvent is distilled off under reduced pressure
  7. customPurification
  8. customhexane/ethyl acetate (1:1) and subsequent crystallization from ethyl acetate

Sources & evidence

ORD record
ord-569dfbb9b5bc43de964999c8fca5665a
Source dataset
uspto-grants-2012_03
Patent number
US08129378B2

Reaction notes

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