Isopropyl iodide → methyl 6-bromo-1-isopropyl-1H-indole-4-carboxylate

HRID 42501Notes

Reaction equation

HRID 42501 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.I[CH:16]([CH3:18])[CH3:17].[H-].[Na+]>CN(C=O)C.O>[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:16]([CH3:18])[CH3:17])[C:9]=2[CH:10]=1

Participants

6

Reactant 3

HCID 6362Isopropyl iodideHCID 24758Sodium hydrideHCID 13770009methyl 6-bromo-1H-indole-4-carboxylate

Product 1

HCID 67466539methyl 6-bromo-1-isopropyl-1H-indole-4-carboxylateYield 55.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of methyl 6-bromo-1H-indole-4-carboxylate (100 g, 393.7 mmol) in DMF (800 mL) was added 2-iodopropane (160 g, 944.8 mmol) followed by portionwise addition of sodium hydride (20.4 g, 511.8 mmol) at 0° C. The reaction mixture was stirred at room temperature for 18 h. Diluted the reaction mixture with cold water and extracted with ethylacetate (200 mL×4), finally organic layer was washed with cold water, brine solution dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford crude, which was purified by column chromatography using silica gel (60-120 mesh) with 5% EtOAC: pet ether as an eluent to afford methyl 6-bromo-1-isopropyl-1H-indole-4-carboxylate (65 g, 55.7%) as a solid. 1H NMR (CDCl3, 400 MHz) δ 1.53 (d, 6H, J=6.4 Hz), 3.973 (s, 3H), 4.598-4.664 (m, 1H), 7.111 (d, 1H, J=2.4 Hz), 7.338 (d, 1H, J=2.8 Hz), 7.711 (s, 1H), 7.987 (s, 1H).

Workup

  1. extractionextracted with ethylacetate (200 mL×4), finally organic layer
  2. washwas washed with cold water, brine solution
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto afford crude, which
  6. customwas purified by column chromatography

Sources & evidence

ORD record
ord-a38905831b2948ca9ec02a14ebc5b982
Source dataset
uspto-grants-2013_09
Patent number
US08536179B2

Reaction notes

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