1-Bromo-3-chloropropane → 1-[4-(3-Chloropropoxy)-3-methylaminophenyl]ethanone

HRID 2184517Notes

Reaction equation

HRID 2184517 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[NH:13][CH3:14].Br[CH2:16][CH2:17][CH2:18][Cl:19]>CN(C)C=O>[Cl:19][CH2:18][CH2:17][CH2:16][O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:12])[CH3:11])=[CH:6][C:5]=1[NH:13][CH3:14]

Participants

5

Reactant 3

HCID 80061-Bromo-3-chloropropaneHCID 24758Sodium hydrideHCID 21960060HCID 21960060, compound

Product 1

HCID 103319421-[4-(3-Chloropropoxy)-3-methylaminophenyl]ethanoneYield 82,742.398%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a stirred suspension of sodium hydride (0.87 g, 18.2 mmol of a 50% oil dispersion) in dimethylformamide (25 ml) under nitrogen and cooled to 0° in an ice-salt bath was added, dropwise, a solution or 1-(4-hydroxy-3-methylamino-phenyl)ethanone (3.0 g, 18.2 mmol) dissolved in dimethylformamide (55 ml) so that the temperature did not rise above 3° C. After the addition was complete, the reaction was stirred for 80 minutes of ambient temperature. The reaction was cooled to 5° C. and a solution of 1-bromo-3-chloropropane (3.1 g, 0.0120 mmol) in dimethylformamide (20 ml) was added dropwise. After this addition was complete, the ice bath was removed and the reaction was stirred at ambient temperature for 2.5 hours. Water (75 ml) was carefully added and after stirring vigorously for 5 minutes, the reaction was left to stand overnight. The aqueous mixture was extracted with ethyl acetate and the ethyl acetate extract was washed with water, dried with MgSO4, and concentrated to yield 3.9 of a dark solid. The compound was purified by preparative HPLC to afford 2.4 g of a beige solid. This was combined with an additional sample (3.8 g was total) and two consecutive recrystallizations from ethanol gave 2.1 g (31%) or 1-[4-(3-chloropropoxy)-3-methyl-aminophenyl]ethanone as a fluffy, beige solid, m.p.=115°-117° C. ANALYSIS: Calculated for C12H16ClNO2: 59. 63%C 6.67%H 5.69%N Found 59.49%C 6.64%H 5.79%N

Workup

  1. temperaturecooled to 0° in an ice-salt bath
  2. additionwas added
  3. customdid not rise above 3° C
  4. additionAfter the addition
  5. temperatureThe reaction was cooled to 5° C.
  6. additionAfter this addition
  7. customthe ice bath was removed
  8. stirringthe reaction was stirred at ambient temperature for 2.5 hours
  9. additionWater (75 ml) was carefully added
  10. stirringafter stirring vigorously for 5 minutes
  11. waitthe reaction was left
  12. waitto stand overnight
  13. extractionThe aqueous mixture was extracted with ethyl acetate
  14. extractionthe ethyl acetate extract
  15. washwas washed with water
  16. dry with materialdried with MgSO4
  17. concentrationconcentrated
  18. customto yield 3.9 of a dark solid
  19. customThe compound was purified by preparative HPLC

Sources & evidence

ORD record
ord-93272c39939e4fed9876dcc95715ffe5
Source dataset
uspto-grants-2002_06
Patent number
USRE037729E1

Reaction notes

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