Toluene → Benzenamine, 4-(4-morpholinyl)-N-[4-(4-morpholinyl)phenyl]-

HRID 324716Notes

Reaction equation

HRID 324716 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:13]=[CH:12][C:10]([NH2:11])=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.[Cl-].[Ca+2].[Cl-].[Cl-].[Al+3].[Cl-].[Cl-].[C:21]1(C)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C1C2C(CCCC2)CCC1>[O:1]1[CH2:2][CH2:3][N:4]([C:7]2[CH:13]=[CH:12][C:10]([NH:11][C:24]3[CH:23]=[CH:22][C:21]([N:4]4[CH2:5][CH2:6][O:1][CH2:2][CH2:3]4)=[CH:26][CH:25]=3)=[CH:9][CH:8]=2)[CH2:5][CH2:6]1

Participants

6

Reactant 4

HCID 1140TolueneHCID 75655Benzenamine, 4-(4-morpholinyl)-HCID 5284359Calcium ChlorideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 9949796Benzenamine, 4-(4-morpholinyl)-N-[4-(4-morpholinyl)phenyl]-Yield 58.4%

Reagents, catalysts & solvents 1

HCID 7044DecalinSolvent

Procedure

In a 300-ml four-necked flask were charged 68 ml of decahydronaphthalene (boiling point: 190° C.) as a solvent and 17.8 g (0.50 mol) of 4-morpholinoaniline, followed by the addition of 15.4 g (0.138 mol) of anhydrous calcium chloride and 18.5 g (0.138 mol) of anhydrous aluminum chloride under stirring. The resulting mixture was reacted at 200 to 210° C. for 5 hours under a nitrogen atmosphere. After cooling, the reaction mixture was added with 76 ml of toluene, followed by charging in 96 g of ice water. The resulting mixture was stirred and allowed to stand, and then, the resulting water layer was separated out. The organic layer was washed successively with 90 ml of a 5% aqueous solution of hydrochloric acid, 60 ml of a 5% aqueous solution of sodium bicarbonate and 60 ml of water. After removal of the organic solvent by distillation under reduced pressure, 48 ml of isopropyl alcohol was added to the residue and the mixture was crystallized overnight at −3 to −8° C. The resulting crystals were collected by filtration, washed with 18 ml of isopropyl alcohol and then dried, whereby 44.9 g (yield: 58.4%) of the title compound was obtained as white crystals. As a result of HPLC. analysis (column: YMC-A-312, detection UV: 280 nm, flow rate: 1.0 ml/min, eluent: acetonitrile/water 7/3), the compound was found to have a purity of 99.7%.

Workup

  1. customThe resulting mixture was reacted at 200 to 210° C. for 5 hours under a nitrogen atmosphere
  2. temperatureAfter cooling
  3. stirringThe resulting mixture was stirred
  4. customthe resulting water layer was separated out
  5. washThe organic layer was washed successively with 90 ml of a 5% aqueous solution of hydrochloric acid, 60 ml of a 5% aqueous solution of sodium bicarbonate and 60 ml of water
  6. customAfter removal of the organic solvent
  7. distillationby distillation under reduced pressure, 48 ml of isopropyl alcohol
  8. additionwas added to the residue
  9. customthe mixture was crystallized overnight at −3 to −8° C
  10. filtrationThe resulting crystals were collected by filtration
  11. washwashed with 18 ml of isopropyl alcohol
  12. customdried

Sources & evidence

ORD record
ord-a8558096e0ee4fe8b4600b5da9b57790
Source dataset
uspto-grants-2001_04
Patent number
US06218576B1

Reaction notes

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