Reacción #77789

Ecuación de reacción

HCl

(4-Bromo-5-fluoro-2-iodo-phenyl)-carbamic acid methyl ester

ethinyltrimethylsilane

KOH

→

5-Bromo-6-fluoro-1H-indole

Rendimiento 80.0%

Disolventes

tert-butanol

triethylamine

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturawas refluxed under argon during 20 min
2. 2
   workup.STIRRINGstirred 1 h at room temperature
3. 3
   Extracciónthe mixture extracted three times with EtOAc
4. 4
   LavadoThe combined organic layers were washed subsequently with H2O and saturated aqueous NaCl
5. 5
   Secadodried with MgSO4
6. 6
   Otrothe solvent was evaporated
7. 7
   OtroThe crude product obtained
8. 8
   Temperaturathe resulting mixture refluxed for 1.5 h
9. 9
   OtroThe solvent was evaporated
10. 10
    LavadoThe organic layer was washed with water
11. 11
    Secadodried with MgSO4
12. 12
    OtroEvaporation of the solvent and column chromatography on silica gel with hexane/EtOAc 9:1

Procedimiento

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).

Fuente