5-Methoxy-2-methylindole → HCID 69315136, compound

HRID 2055727Notes

Reaction equation

HRID 2055727 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([CH3:12])=[CH:6]2.C([Li])CCC.[Br:18][C:19]([CH3:24])([CH3:23])[C:20](Br)=[O:21]>C1COCC1.C1(C)C=CC=CC=1.[Cl-].[Cl-].[Zn+2]>[Br:18][C:19]([CH3:24])([CH3:23])[C:20]([C:6]1[C:5]2[C:9](=[CH:10][CH:11]=[C:3]([O:2][CH3:1])[CH:4]=2)[NH:8][C:7]=1[CH3:12])=[O:21]

Participants

7

Reactant 3

HCID 706425-Methoxy-2-methylindoleHCID 886852-Bromo-2-methylpropionyl bromideHCID 178418339Butyllithium

Product 1

HCID 69315136HCID 69315136, compoundYield 41.6%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To an ice-cooled solution of 5-methoxy-2-methylindole (2.5 g, 15.5 mmol) in THF (30 mL) was added n-butyllithium (2.5M solution in hexanes: 6.25 mL, 16.28 mmol) in a dropwise manner. After 20 minutes, ZnCl2 (1M solution in ether; 15.5 mL, 1.0 eq.) was added and the resulting solution stirred at 0° C. for 2 hrs. The solvent was then removed and the residue dissolved in anhydrous toluene (30 mL) to which 2-bromoisobutyryl bromide (1.93 mL, 16.28 mmol) was added and the mixture stirred at ambient temperature for 24 hrs. The solution was partitioned between 1M HCl (100 mL) and EtOAc (100 mL), the organic phase separated, washed with water, dried (MgSO4), filtered and evaporated to dryness. The residue was purified by column chromatography (0 to 25% EtOAc:hexanes) to afford 2.0 g of 2-bromo-1-(5-methoxy-2-methyl-1H-indol-3-yl)-2-methyl-propan-1-one as a yellow solid. 1H NMR (500 MHz, CDCl3) δ 8.52 (1H, s), 7.97 (1H, d, J=2.2 Hz), 7.21 (1H, d, J=8.8 Hz), 6.87 (1H, dd, J=8.8, 2.2 Hz), 3.91 (3H, s), 2.67 (3H, s), 2.13 (6H, s).

Workup

  1. customThe solvent was then removed
  2. additionwas added
  3. stirringthe mixture stirred at ambient temperature for 24 hrs
  4. customThe solution was partitioned between 1M HCl (100 mL) and EtOAc (100 mL)
  5. customthe organic phase separated
  6. washwashed with water
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customThe residue was purified by column chromatography (0 to 25% EtOAc:hexanes)

Sources & evidence

ORD record
ord-7c4b64a7f0314ad49ac00e78de0a42ec
Source dataset
uspto-grants-2008_02
Patent number
US07332516B2

Reaction notes

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