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

HRID 1371347Notes

Reaction equation

HRID 1371347 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 2 l of N-methylpyrrolidone (NNP). 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., 1.71 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., 1.71 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-b286d978cb594aea86be597bd9496c38
Source dataset
uspto-grants-2007_01
Patent number
US07157456B2

Reaction notes

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