Dimethylformamide → 4-(2-(4-Bromophenoxy)ethyl)morpholine

HRID 545160Notes

Reaction equation

HRID 545160 reaction equation
ClC[CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.[Br:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[Br:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:3][CH2:4][N:5]2[CH2:10][CH2:9][O:8][CH2:7][CH2:6]2)=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 78084-BromophenolHCID 11430Potassium CarbonateHCID 958344-(3-Chloropropyl)morpholine

Product 1

HCID 20538154-(2-(4-Bromophenoxy)ethyl)morpholineYield 2,180.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
62.5 °C

Procedure

A 50 L jacketed reactor equipped with a reflux condenser and temperature probe was charged with 4-(3-chloropropyl)morpholine (2.44 kg, 0.54 mol), 4-bromophenol (2.27 kg, 0.54 mol, 1.0 equiv.), powdered potassium carbonate (6.331 kg, 1.88 mol, 3.50 equiv.), and DMF (12.2 L) and stirred. The reaction mixture was then heated to 60-65° C. and stirred overnight. After 17.5 h, the reaction mixture was cooled to 20-25° C. The reaction mixture was charged to a different reactor equipped with bottom valve for the work-up. While maintaining a temperature between 20-30° C., DI water (48.7 L) was charged to the reactor. The phases were separated. The aqueous layer was extracted with MTBE (3×24.4 L). To the combined organics, DI water (18.3 L) and then 6M sodium hydroxide (18.2 L) were added. The mixture was stirred for 2-5 minutes and the phases were separated. The organic phase was washed with water (24.4 L) and brine (24.4 L), dried over magnesium sulfate, filtered, and concentrated to give 3370 g of a yellow oil (89% crude yield, 99.4% AUC by HPLC).

Workup

  1. customequipped with a reflux condenser
  2. stirringstirred overnight
  3. temperaturethe reaction mixture was cooled to 20-25° C
  4. additionThe reaction mixture was charged to a different reactor
  5. customequipped with bottom valve for the work-up
  6. temperatureWhile maintaining a temperature between 20-30° C.
  7. customThe phases were separated
  8. extractionThe aqueous layer was extracted with MTBE (3×24.4 L)
  9. additionTo the combined organics, DI water (18.3 L) and then 6M sodium hydroxide (18.2 L) were added
  10. stirringThe mixture was stirred for 2-5 minutes
  11. customthe phases were separated
  12. washThe organic phase was washed with water (24.4 L) and brine (24.4 L)
  13. dry with materialdried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-cec5b6cf6763429abc7cbad9a597a948
Source dataset
uspto-grants-2011_05
Patent number
US07935697B2

Reaction notes

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