Morpholine → (3,4-Dinitrophenyl)(morpholino)methanone

HRID 1639640Notes

Reaction equation

HRID 1639640 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1[N+:13]([O-:15])=[O:14])[C:7]([OH:9])=O)([O-:3])=[O:2].S(Cl)(Cl)=O.C(N(CC)CC)C.[NH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1>O.CN(C)C=O.O1CCCC1>[N+:1]([C:4]1[CH:5]=[C:6]([C:7]([N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)=[O:9])[CH:10]=[CH:11][C:12]=1[N+:13]([O-:15])=[O:14])([O-:3])=[O:2]

Participants

8

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 107093,4-Dinitrobenzoic acidHCID 24386Thionyl Chloride

Product 1

HCID 13043973(3,4-Dinitrophenyl)(morpholino)methanoneYield 97.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
67.5 °C

Procedure

3,4-Dinitrobenzoic acid (1.000 Kg, 4.71 mol, 1.0 wt), tetrahydrofuran (10.00 L, 10.0 vol), and dimethylformamide (0.010 L, 0.01 vol) were charged to a flask under nitrogen. Thionyl chloride (0.450 L, 6.16 mol, 0.45 vol) was added at 20 to 30° C. and the reaction mixture was heated to 65 to 70° C. Reaction completion was determined by 1H NMR analysis (d6-DMSO), typically in 3 hours. The reaction mixture was cooled to 0 to 5° C. and triethylamine (1.25 L, 8.97 mol, 1.25 vol) was added at 0 to 10° C. Morpholine (0.62 L, 7.07 mol, 0.62 vol) was charged to the reaction mixture at 0 to 10° C. and the slurry was stirred for 30 minutes at 0 to 10° C. Reaction completion was determined by 1H NMR analysis (d6-DMSO). The reaction mixture was warmed to 15 to 20° C. and water (4.0 L, 4.0 vol) was added. This mixture was then charged to a 40 L flange flask containing water (21.00 L, 21.0 vol) at 15 to 25° C. to precipitate the product. The flask contents were cooled to and aged at 0 to 5° C. for 1 hour and the solids were collected by filtration. The filter-cake was washed with water (4×5.00 L, 4×5.0 vol) and the pH of the final wash was found to be pH 7. The wet filter-cake was analysed by 1H NMR for the presence of triethylamine hydrochloride. The filter-cake was dried at 40 to 45° C. under vacuum until the water content by KF<0.2% w/w, to yield (3,4-dinitrophenyl)-morpholin-4-yl-methanone (1.286 Kg, 97.0%, KF 0.069% w/w) as a yellow solid.

Workup

  1. customReaction completion
  2. temperatureThe reaction mixture was cooled to 0 to 5° C.
  3. customReaction completion
  4. temperatureThe reaction mixture was warmed to 15 to 20° C.
  5. additionThis mixture was then charged to a 40 L flange flask
  6. customto precipitate the product
  7. temperatureThe flask contents were cooled to and
  8. waitaged at 0 to 5° C. for 1 hour
  9. filtrationthe solids were collected by filtration
  10. washThe filter-cake was washed with water (4×5.00 L, 4×5.0 vol)
  11. washthe pH of the final wash
  12. filtrationThe wet filter-cake
  13. dry with materialThe filter-cake was dried at 40 to 45° C. under vacuum until the water content by KF<0.2% w/w

Sources & evidence

ORD record
ord-6ae6e616934f428db528f904bd8da861
Source dataset
uspto-grants-2012_02
Patent number
US08110573B2

Reaction notes

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