2-Bromopropane → methyl 6-bromo-1-isopropyl-1H-indole-4-carboxylate

HRID 516656Notes

Reaction equation

HRID 516656 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:5]2[CH:6]=[CH:7][NH:8][C:9]=2[CH:10]=1.[H-].[Na+].Br[CH:18]([CH3:20])[CH3:19].CCCCCC>CN(C)C=O.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:5]2[CH:6]=[CH:7][N:8]([CH:18]([CH3:20])[CH3:19])[C:9]=2[CH:10]=1

Participants

7

Reactant 4

HCID 63582-Bromopropane2×HCID 8058HexaneHCID 24758Sodium hydride2×HCID 13770009methyl 6-bromo-1H-indole-4-carboxylate

Product 1

HCID 67466539methyl 6-bromo-1-isopropyl-1H-indole-4-carboxylateYield 43.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a cooled (0° C.) solution of methyl 6-bromo-1H-indole-4-carboxylate (1.0 g, 3.94 mmol) solid in N,N-dimethylformamide (25 mL) was added sodium hydride (0.173 g, 4.33 mmol). The reaction was stirred for 15 min, at which time 2-bromopropane (0.554 mL, 5.90 mmol) was added. The reaction was then allowed to warm to RT and was maintained overnight. LCMS showed about 25% starting material remaining. The reaction was heated at 45° C. for 4 h, but no further conversion was noted. The reaction vessel was put back into an ice bath and stirred for 15 min. Then excess NaH (60%) was added, stirred for 10 min, and then 2-bromopropane (excess) was added. The ice bath was removed and the reaction stirred for 1 h. Approximately half of the reaction volume was removed in vacuo and poured into saturated NH4Cl (200 mL). This was extracted with ether (2 x) and the combined organics were washed with brine, dried (MgSO4), and concentrated. Purification by column chromatography (80 g Isco silica column; Gradient B: 5-25%, A: hexane, B: ethyl acetate) gave methyl 6-bromo-1-(1-methylethyl)-1H-indole-4-carboxylate (0.53 g, 1.718 mmol, 43.7% yield).

Workup

  1. additionwas added
  2. temperaturewas maintained overnight
  3. temperatureThe reaction was heated at 45° C. for 4 h
  4. customThe reaction vessel was put back into an ice bath
  5. stirringstirred for 10 min
  6. customThe ice bath was removed
  7. stirringthe reaction stirred for 1 h
  8. customApproximately half of the reaction volume was removed in vacuo
  9. additionpoured into saturated NH4Cl (200 mL)
  10. extractionThis was extracted with ether (2 x)
  11. washthe combined organics were washed with brine
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated
  14. customPurification by column chromatography (80 g Isco silica column

Sources & evidence

ORD record
ord-331ccd5f82b14d579433091090eb9a5e
Source dataset
uspto-grants-2015_08
Patent number
US09114141B2

Reaction notes

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