1-Bromo-3-chloropropane → 1-{3-{Bis[4-(methoxymethoxy)phenyl]methyl}-1-(3-chloropropyl)indol-2-ylcarbonyl}-4-(2-chlorophenyl)piperazine

HRID 442878Notes

Reaction equation

HRID 442878 reaction equation
[CH3:1][O:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]([C:36]2[CH:41]=[CH:40][C:39]([O:42][CH2:43][O:44][CH3:45])=[CH:38][CH:37]=2)[C:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[NH:14][C:13]=2[C:21]([N:23]2[CH2:28][CH2:27][N:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[Cl:35])[CH2:25][CH2:24]2)=[O:22])=[CH:7][CH:6]=1.[H-].[Na+].Br[CH2:49][CH2:50][CH2:51][Cl:52].[Cl-].[NH4+]>CN(C)C=O.O>[CH3:1][O:2][CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([CH:11]([C:36]2[CH:37]=[CH:38][C:39]([O:42][CH2:43][O:44][CH3:45])=[CH:40][CH:41]=2)[C:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]([CH2:49][CH2:50][CH2:51][Cl:52])[C:13]=2[C:21]([N:23]2[CH2:28][CH2:27][N:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[Cl:35])[CH2:25][CH2:24]2)=[O:22])=[CH:9][CH:10]=1

Participants

7

Reactant 4

HCID 80061-Bromo-3-chloropropane2×HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 158589011-{3-{Bis[4-(methoxymethoxy)phenyl]methyl}indol-2-ylcarbonyl}-4-(2-chlorophenyl)piperazine

Product 1

HCID 701468231-{3-{Bis[4-(methoxymethoxy)phenyl]methyl}-1-(3-chloropropyl)indol-2-ylcarbonyl}-4-(2-chlorophenyl)piperazineYield 95.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of Compound 1 (5.0 g, 7.99 mmol) obtained in Example 1 in 50 ml of N,N-dimethylformamide was portionwise added sodium hydride (60%. in oil, 351 mg, 8.78 mmol) with stirring at room temperature, and 1-bromo-3-chloropropane (0.87 ml, 8.78 mmol) was added thereto, followed by stirring at room temperature for 4 hours. 1-Bromo-3-chloropropane (0.16 ml, 1.62 mmol) was added thereto and the mixture was stirred further for 4.5 hours. The reaction mixture was neutralized with a saturated aqueous solution of ammonium chloride, and water was added thereto followed by extraction with ethyl acetate. The resulting organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried over magnesium sulfate, and the solvent was distilled off under reduced pressure to give 6.5 g of a crude product. The obtained crude product was purified with silica gel column chromatography (ethyl acetate/hexane=1/3-1/1) to give 5.35 g (yield: 95%) of the title compound.

Workup

  1. stirringby stirring at room temperature for 4 hours
  2. stirringthe mixture was stirred further for 4.5 hours
  3. additionwas added
  4. extractionthereto followed by extraction with ethyl acetate
  5. washThe resulting organic layer was washed with water
  6. dry with materiala saturated aqueous solution of sodium chloride and dried over magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. customto give 6.5 g of a crude product
  9. customThe obtained crude product
  10. customwas purified with silica gel column chromatography (ethyl acetate/hexane=1/3-1/1)

Sources & evidence

ORD record
ord-a97d063ae174447dba9e5c9e472fc563
Source dataset
uspto-grants-1999_04
Patent number
US05891902

Reaction notes

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