Methyl iodide → Indole

HRID 483410Notes

Reaction equation

HRID 483410 reaction equation
ClC1C=CC(C[N:7]2[C:15]3[C:10](=[CH:11][C:12](F)=[CH:13][CH:14]=3)[C:9](SC)=[C:8]2CC(OCC)=O)=CC=1.C[Si](C)(C)[N-][Si](C)(C)C.[K+].CI.S(=O)(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.CCOCC.O1CCCC1>[NH:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[CH:8]1

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 516919Sodium BisulfateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 15035365HCID 15035365, compound

Product 1

HCID 798Indole

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a cold (-78°), stirred solution of 560 mg of ethyl 1-(p-chlorobenzyl)-5-fluoro-3-methylthioindole-2-acetate from Example 3 in 6 75 mL dry tetrahydrofuran, under argon, was added 2.72 mL of a 0.63 M solution of potassium hexamethyldisilazide in toluene. After 2 h at -78°, 123 μL of methyl iodide was added and the mixture stirred at -78° for 30 min and 0° for 1 h. 10% aqueous sodium bisulfate and ether were then added. The organic layer was separated, washed with 10% aqueous sodium bisulfate, water and brine and dried over MgSO4. Filtration and concentration gave a pale yellow oil which was purified by flash chromatography on silica gel. Elution with a mixture of hexane ethyl acetate (85:15) gave an indole derivative, mp 131°-132°.

Workup

  1. customThe organic layer was separated
  2. washwashed with 10% aqueous sodium bisulfate, water and brine
  3. dry with materialdried over MgSO4
  4. filtrationFiltration and concentration
  5. customgave a pale yellow oil which
  6. customwas purified by flash chromatography on silica gel
  7. washElution
  8. additionwith a mixture of hexane ethyl acetate (85:15)

Sources & evidence

ORD record
ord-f034448fe5f0437abeac8abbcdc484ff
Source dataset
uspto-grants-1993_07
Patent number
US05225421

Reaction notes

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