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

HRID 2394688Notes

Reaction equation

HRID 2394688 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].C(N)=O>CN(C)C=O.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

7

Reactant 4

HCID 713FormamideHCID 80061-Bromo-3-chloropropaneHCID 24758Sodium hydrideHCID 12225608HCID 12225608, compound

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

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 dimethy]formamide (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-85aba3c75e9541aeb40a1a059b83c209
Source dataset
uspto-grants-1998_09
Patent number
US05811435

Reaction notes

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