Hydrochloric Acid → 5-bromo-6-fluoro-1H-indole

HRID 49511Notes

Reaction equation

HRID 49511 reaction equation
CO[C:3](=O)[NH:4][C:5]1[CH:10]=[C:9]([F:11])[C:8]([Br:12])=[CH:7][C:6]=1I.[C:15]([Si](C)(C)C)#C.Cl.[OH-].[K+]>C(N(CC)CC)C.C(O)(C)(C)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Br:12][C:8]1[CH:7]=[C:6]2[C:5](=[CH:10][C:9]=1[F:11])[NH:4][CH:3]=[CH:15]2

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 66111TrimethylsilylacetyleneHCID 57543465Methyl N-(4-bromo-5-fluoro-2-iodophenyl)carbamate

Product 1

HCID 116871455-bromo-6-fluoro-1H-indoleYield 80%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6386tert-ButanolSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 70 mg (0.1 mmol) Pd(PPh3)2Cl2 and 27 mg (0.142 mmol) CuI in triethylamine was refluxed under argon during 20 min, cooled to 0° C., treated with 7 g (0.019 mmol) (4-Bromo-5-fluoro-2-iodo-phenyl)-carbamic acid methyl ester, stirred 10 min at room temperature, treated with 2.95 (0.021 mmol) ethinyltrimethylsilane, and stirred 1 h at room temperature. 2M aqueous HCl and ice were added and the mixture extracted three times with EtOAc. The combined organic layers were washed subsequently with H2O and saturated aqueous NaCl, dried with MgSO4 and the solvent was evaporated. The crude product obtained was dissolved in 50 ml tert-butanol, treated with 3.2 g (0.023 mol) KOH and the resulting mixture refluxed for 1.5 h. The solvent was evaporated and the residue distributed between icy water and Et2O. The organic layer was washed with water and dried with MgSO4. Evaporation of the solvent and column chromatography on silica gel with hexane/EtOAc 9:1 gave of 3.2 g (80%) 5-Bromo-6-fluoro-1H-indole, MS: 213 (M, 1Br).

Workup

  1. temperaturewas refluxed under argon during 20 min
  2. stirringstirred 1 h at room temperature
  3. extractionthe mixture extracted three times with EtOAc
  4. washThe combined organic layers were washed subsequently with H2O and saturated aqueous NaCl
  5. dry with materialdried with MgSO4
  6. customthe solvent was evaporated
  7. customThe crude product obtained
  8. temperaturethe resulting mixture refluxed for 1.5 h
  9. customThe solvent was evaporated
  10. washThe organic layer was washed with water
  11. dry with materialdried with MgSO4
  12. customEvaporation of the solvent and column chromatography on silica gel with hexane/EtOAc 9:1

Sources & evidence

ORD record
ord-9258796dcd87477d96eed30d90f745c5
Source dataset
uspto-grants-2004_03
Patent number
US06706751B2

Reaction notes

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