Water → 1-[4-(3-Chloropropoxy)-3-dimethylaminophenyl]ethanone

HRID 1638013Notes

Reaction equation

HRID 1638013 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:12])[CH3:11])=[CH:6][C:5]=1[N:13]([CH3:15])[CH3:14].Br[CH2:17][CH2:18][CH2:19][Cl:20].O>CN(C)C=O>[Cl:20][CH2:19][CH2:18][CH2:17][O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:12])[CH3:11])=[CH:6][C:5]=1[N:13]([CH3:14])[CH3:15]

Participants

6

Reactant 4

HCID 962WaterHCID 80061-Bromo-3-chloropropaneHCID 24758Sodium hydrideHCID 12225608HCID 12225608, compound

Product 1

HCID 101064281-[4-(3-Chloropropoxy)-3-dimethylaminophenyl]ethanoneYield 179%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
3 °C

Procedure

To a suspension of sodium hydride (2.3 g, 48.5 mmol of 50% oil dispersion) with dimethylformamide (75 ml), and cooled to 3° C. in an ice-salt bath and under a stream of nitrogen was added, dropwise, 1-(4-hydroxy-3-dimethylaminophenyl)ethanone (8.7 g, 48.5 mmol) dissolved in dimethylformamide (150 ml) so that the temperature did not go over 7° C. After the addition was over, the bath was removed and the reaction was stirred at ambient temperature for 45 minutes. The ice bath was reapplied and a solution of 1-bromo-3-chloropropane (8.4 g, 53.4 mmol) in dimethylformamide (25 ml) was added dropwise. After the addition was complete, the reaction was stirred for 18 hours at ambient temperature under nitrogen. The reaction was chilled to 7° C. in an ice bath and water (200 ml) was carefully added. After stirring for 5 minutes, the aqueous mixture was extracted with ethyl acetate (5×200 ml). The ethyl acetate extract was washed with water (2×50 ml), dried with MgSO4, and concentrated to yield 22.2 g of a black oily liquid. The compound was purified by prep HPLC, and combination of appropriate fractions gave 5.0 g of brown oil.

Workup

  1. additionwas added
  2. customdid not go over 7° C
  3. additionAfter the addition
  4. customwas removed
  5. additionAfter the addition
  6. stirringthe reaction was stirred for 18 hours at ambient temperature under nitrogen
  7. temperatureThe reaction was chilled to 7° C. in an ice bath
  8. stirringAfter stirring for 5 minutes
  9. extractionthe aqueous mixture was extracted with ethyl acetate (5×200 ml)
  10. extractionThe ethyl acetate extract
  11. washwas washed with water (2×50 ml)
  12. dry with materialdried with MgSO4
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-a69667609c904e93b5cb3e35cda3219c
Source dataset
uspto-grants-2000_03
Patent number
US06043240

Reaction notes

Loading…