Sodium Iodide → (4-Bromo-3-methyl-phenyl)-(2-morpholin-4-yl-ethyl)-amine

HRID 2216147Notes

Reaction equation

HRID 2216147 reaction equation
[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[CH3:9].Cl[CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.C([O-])([O-])=O.[K+].[K+].[Na+].[I-]>CS(C)=O.CCOC(C)=O>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:4][C:3]=1[CH3:9]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 233594-Bromo-3-methylanilineHCID 767274-(2-Chloroethyl)morpholine

Product 1

HCID 21886410(4-Bromo-3-methyl-phenyl)-(2-morpholin-4-yl-ethyl)-amineYield 32.5%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Bromo-3-methylaniline (0.96 gm, 5.14 mmol), 4-(2-chloro-ethyl)-morpholine (1 gm, 5.4 mmol), K2CO3 (1.5 gm, 10.8 mmol), and NaI (0.81 gm, 5.4 mmol) were suspended in DMSO (10 mL) and the mixture was stirred vigorously at reflux for 12 h. The mixture was cooled, diluted with EtOAc, and washed with saturated NaHCO3. The organic layer was washed with another portion of NaHCO3, brine (50 mL), and was dried over MgSO4. Removal of the solvents in vacuo followed by flash chromatography of the residue (Biotage Flash System—40 M SiO2 column, 10% EtOAc in hexanes to 100% EtOAc) yielded the product (500 mg, 31%) as a tan oil. 1H-NMR (CDCl3; 400 MHz): δ 7.36 (d, 1H, J=8.6 Hz), 6.61 (d, 1H, J=2.8 Hz), 6.43 (dd, 1H, d, 8.6, 2.8 Hz), 4.36 (br s, 1H), 3.80 (t, 4H, J=4.6 Hz), 3.20 (t, 2H, J=5.8 Hz), 2.69 (t, 2H, J=6.0 Hz), 2.54 (t, 4H, J=4.4 Hz), 2.40 (s, 3H). ESI-MS (m/z): Calcd. for C13H19BrN2O: 299.2; found: 299.1, 301.1.

Workup

  1. temperatureat reflux for 12 h
  2. temperatureThe mixture was cooled
  3. washwashed with saturated NaHCO3
  4. washThe organic layer was washed with another portion of NaHCO3, brine (50 mL)
  5. dry with materialwas dried over MgSO4
  6. customRemoval of the solvents in vacuo

Sources & evidence

ORD record
ord-15729a239ab343ad8f79f5cbbe49cfc9
Source dataset
uspto-grants-2006_09
Patent number
US07109354B2

Reaction notes

Loading…