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

HRID 42398Notes

Reaction equation

HRID 42398 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×) 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×)
  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-5f90fb9b74d647d791676d7cca30aaa1
Source dataset
uspto-grants-2013_09
Patent number
US08536179B2

Reaction notes

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