2-Methylindole → 1-(4-bromobutyl)-3-methyl-1H-indole

HRID 1176299Notes

Reaction equation

HRID 1176299 reaction equation
C[C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2.[H-].[Na+].[Br:13][CH2:14][CH2:15][CH2:16][CH2:17]Br.[CH3:19]N1C(=O)N(C)CCC1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Br:13][CH2:14][CH2:15][CH2:16][CH2:17][N:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:10]([CH3:19])=[CH:2]1

Participants

6

Reactant 4

HCID 72242-MethylindoleHCID 80561,4-DibromobutaneHCID 24758Sodium hydrideHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-

Product 1

HCID 685006891-(4-bromobutyl)-3-methyl-1H-indole

Reagents, catalysts & solvents 1

HCID 67553Tetrabutylammonium IodideCatalyst

Procedure

The solution of 5.0 g of 2-methylindole in 70 ml of DMPU is admixed with stirring at 0° C. with 3.30 g of sodium hydride dispersion (60%) and stirred at room temperature over 2 hours. Subsequently, 20 ml of 1,4-dibromobutane and 1.40 g of tetrabutylammonium iodide are added (exothermic reaction). The mixture is stirred at room temperature over 20 hours. The reaction mixture is poured onto water (200 ml) and extracted with tert-butyl methyl ether (2×200 ml). The organic phases are washed successively with water (4×200 ml) and brine (1×200 ml), dried over sodium sulphate, filtered and concentrated by evaporation. The excess of 1,4-dibromobutane is evaporated out of the residue under high vacuum and the title compound is obtained as a slightly yellowish oil by means of flash chromatography (SiO2 60F). Rf=0.79 (1:1 EtOAc-heptane); Rt=5.43.

Workup

  1. custom(exothermic reaction)
  2. stirringThe mixture is stirred at room temperature over 20 hours
  3. additionThe reaction mixture is poured onto water (200 ml)
  4. extractionextracted with tert-butyl methyl ether (2×200 ml)
  5. washThe organic phases are washed successively with water (4×200 ml) and brine (1×200 ml)
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated by evaporation
  9. customThe excess of 1,4-dibromobutane is evaporated out of the residue under high vacuum

Sources & evidence

ORD record
ord-87b186e6390a4b8192a179533f2dd62f
Source dataset
uspto-grants-2010_11
Patent number
US07842688B2

Reaction notes

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