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

HRID 2379937Notes

Reaction equation

HRID 2379937 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×

Procedure

To a suspension of sodium hydride (2.3 g, 0.0485 mol of 50% oil dispersion) with dimethylformamide (75 ml), and cooled to 3° in an ice-salt bath and under a stream of nitrogen was added, dropwise, 1-(4-hydroxy-3-dimethylaminophenyl)ethanone (8.7 g, 0.0485 mol) dissolved in dimethylformamide (150 ml) so that the temperature did not go over 7°. 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, 0.0534 mol) 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° 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. temperaturecooled to 3° in an ice-salt bath and under a stream of nitrogen
  2. additionwas added
  3. customdid not go over 7°
  4. additionAfter the addition
  5. customwas removed
  6. additionAfter the addition
  7. stirringthe reaction was stirred for 18 hours at ambient temperature under nitrogen
  8. temperatureThe reaction was chilled to 7° in an ice bath
  9. stirringAfter stirring for 5 minutes
  10. extractionthe aqueous mixture was extracted with ethyl acetate (5×200 ml)
  11. extractionThe ethyl acetate extract
  12. washwas washed with water (2×50 ml)
  13. dry with materialdried with MgSO4
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-6b7cc21ecb9246dcbfd846f802a6cb5d
Source dataset
uspto-grants-1994_11
Patent number
US05364866

Reaction notes

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