Hydrochloric Acid → Methyl (2,6-dimethyl-1H-indol-3-yl)acetate

HRID 1069549Notes

Reaction equation

HRID 1069549 reaction equation
[CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[C:6]([CH3:11])[CH:5]=2.C([Li])CCC.Br[CH2:18][C:19]([O:21][CH3:22])=[O:20].Cl>C1COCC1.CCCCCC.CCOCC.[Cl-].[Cl-].[Zn+2].CCOC(C)=O>[CH3:22][O:21][C:19](=[O:20])[CH2:18][C:10]1[C:9]2[C:4](=[CH:5][C:6]([CH3:11])=[CH:7][CH:8]=2)[NH:3][C:2]=1[CH3:1]

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 60984Methyl bromoacetateHCID 1385512,6-DimethylindoleHCID 178418339Butyllithium

Product 1

HCID 54107367Methyl (2,6-dimethyl-1H-indol-3-yl)acetateYield 73%

Reagents, catalysts & solvents 5

HCID 3007855ZincchlorideCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a cooled solution of 2.9 g (0.02 mol) of 2,6-dimethyl-1H-indole in 40 ml of THF was added 12.5 mL (0.02 mol) of a 1.6M solution of n-butyl lithium in hexane keeping the temperature below 10° C. with an ice-ethanol bath. After 0.25 hours, 20.0 ml (0.0277 mol) of a 1M solution of ZnCl2 in ether was added. The cooling bath was removed and the mixture stirred for 2 hours, then concentrated at reduced pressure to a wax which was dissolved in 40 ml of toluene. To this solution was added 1.89 ml (0.02 mol) of methyl 2-bromoacetate, the mixture was stirred 24 hours and poured into 100 ml of 1N HCl and 100 ml of EtOAc. The organic layer was washed twice with water, dried (Na2SO4), and concentrated at reduced pressure. The residue was chromatographed on silica and eluted with 10% EtOAc/toluene to give 3.17 g (73%) of 2,6-dimethyl-1H-indole-3-acetic acid methyl ester as an oil.

Workup

  1. customThe cooling bath was removed
  2. concentrationconcentrated at reduced pressure to a wax which
  3. dissolutionwas dissolved in 40 ml of toluene
  4. stirringthe mixture was stirred 24 hours
  5. washThe organic layer was washed twice with water
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated at reduced pressure
  8. customThe residue was chromatographed on silica
  9. washeluted with 10% EtOAc/toluene

Sources & evidence

ORD record
ord-aef8801e744f4e13b6011ce38bbefe1c
Source dataset
uspto-grants-2001_06
Patent number
US06252084B1

Reaction notes

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