Potassium Iodide → HCID 66898628, compound

HRID 2369862Notes

Reaction equation

HRID 2369862 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH3:15].[H-].[Na+].[I-].[K+].Br[CH2:21][CH:22]([O:25][CH3:26])[O:23][CH3:24]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([O:13][CH3:14])=[O:12])[CH:10]=1)[N:7]([CH2:21][CH:22]([O:25][CH3:26])[O:23][CH3:24])[CH:6]=[C:5]2[CH3:15]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 24758Sodium hydrideHCID 816722-Bromo-1,1-dimethoxyethaneHCID 66898634HCID 66898634, compound

Product 1

HCID 66898628HCID 66898628, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of methyl 5-chloro-3-methyl-1H-indole-7-carboxylate (1.4 g, 4.5 mmol) from Step B above in DMF (10 ml) was added sodium hydride (313 mg, 7.8 mmol) in portions. The mixture was stirred at room temperature for 1 h, then potassium iodide (60 mg, 0.4 mmol) and 2-bromo-1,1-dimethoxyethane (2.1 ml, 17.9 mmol) were added. The mixture was heated to 80° C. for 15 h. After cooling to room temperature, the reaction was quenched with saturated aqueous ammonium chloride, extracted with ethyl acetate (3×), washed with brine, filtered, and dried over sodium sulfate. The filtrate was concentrated under reduced pressure and the residue purified by column chromatography (silica gel, 70:30 hexanes/ethyl acetate) to afford methyl 5-chloro-1-(2,2-dimethoxyethyl)-3-methyl-1H-indole-7-carboxylate (908 mg, 68%) as a semitransparent liquid: 1H NMR (500 MHz, CDCl3) δ 7.64 (d, J=1.0 Hz, 1H), 7.61 (d, J=1.0 Hz, 1H), 6.94 (s, 1H), 4.62 (t, J=5.0 Hz, 1H), 4.39 (d, J=5.0 Hz, 1H), 3.96 (s, 3H), 3.30 (s, 6H), 2.27 (s, 3H).

Workup

  1. temperatureThe mixture was heated to 80° C. for 15 h
  2. temperatureAfter cooling to room temperature
  3. customthe reaction was quenched with saturated aqueous ammonium chloride
  4. extractionextracted with ethyl acetate (3×)
  5. washwashed with brine
  6. filtrationfiltered
  7. dry with materialdried over sodium sulfate
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe residue purified by column chromatography (silica gel, 70:30 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-7d96e089db944cdf9a99761a9ef7d2fe
Source dataset
uspto-grants-2014_04
Patent number
US08710046B2

Reaction notes

Loading…