4-Bromobutyronitrile → HCID 23003165, compound

HRID 396203Notes

Reaction equation

HRID 396203 reaction equation
[Cl:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:3]=1[CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][CH:10]=[CH:9]2.[H-].[Na+].Br[CH2:23][CH2:24][CH2:25][C:26]#[N:27]>CN(C)C=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:3]=1[CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH2:23][CH2:24][CH2:25][C:26]#[N:27])[CH:10]=[CH:9]2.[Cl:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:3]=1[CH2:4][O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH:24]([CH3:23])[CH2:25][C:26]#[N:27])[CH:10]=[CH:9]2

Participants

7

Reactant 3

HCID 214124-BromobutyronitrileHCID 24758Sodium hydrideHCID 23003167HCID 23003167, compound

Product 2

HCID 23003160HCID 23003160, compoundYield 15%HCID 23003165HCID 23003165, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-(2,6-dichlorobenzyloxy)-1H-indole (2.0 g, 6.85 mmol) in dimethylformamide (30 mL) at ambient temperature was added sodium hydride (0.41 g, 10.3 mmol, 60% in mineral oil). After stirring at ambient temperature for 1 h, 4-bromobutyronitrile (1.01 g, 0.68 mL, 6.85 mmol) was added followed by the addition of tetrabutylammonium iodide (0.25 g, 0.68 mmol). After stirring at room temperature for 24 h, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine and dried (Na2SO4). Purification by flash column chromatography (silica gel, hexanes/ethyl acetate) yielded a mixture (1.37 g total weight) of desired product (85%) and undesired product 3-[5-(2,6-dichlorobenzyloxy)indole-1-yl]butyronitrile (15%). The two component mixture (0.12 g total weight) was treated with sodium methoxide (catalytic) in methanol/THF at room temperature for 16 h. The undesired product was decomposed and purification by flash column chromatography (silica gel, hexanes/ethyl acetate) afforded the desired product as a clear oil (0.1 g). MS(ES) m/e 359.0 [M+H]+.

Workup

  1. stirringAfter stirring at room temperature for 24 h
  2. customthe reaction mixture was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried (Na2SO4)
  5. customPurification by flash column chromatography (silica gel, hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-3853c0bc048442e8b654be07635c69cb
Source dataset
uspto-grants-2003_08
Patent number
US06608059B1

Reaction notes

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