Reacción #69952

Ecuación de reacción

trimethyl borate

sodium carbonate

butyl lithium

hexane

triphenylphosphine

4-chloro-iodobenzene

3,5-dibromo-2-ethyl-thiophene

→

3-bromo-5-(4-chlorophenyl)-2-ethyl-thiophene

Rendimiento 75.0%

Disolventes

THF

diethyl ether

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGThe reaction is stirred at −78° C. for 30 minutes
2. 2
   Temperaturato warm to room temperature
3. 3
   workup.STIRRINGstirred for a further 60 minutes
4. 4
   Temperaturathe reaction is heated
5. 5
   Temperaturato reflux for 3 hours
6. 6
   OtroThe cooled reaction mixture
7. 7
   Otrois partitioned between ether (250 ml) and water (300 ml)
8. 8
   OtroThe organic layer is separated
9. 9
   Secadodried over magnesium sulphate
10. 10
    Filtraciónfiltered
11. 11
    Otroevaporated under reduced pressure
12. 12
    OtroThe residue is therefore purified by flash chromatography on silica gel

Procedimiento

To a solution of 3,5-dibromo-2-ethyl-thiophene (3.28 g, 12.15 mmol) in diethyl ether (50 ml) at −78° C. under N2 is added, slowly, 2.5M butyl lithium in hexane solution (4.86 ml, 12.15 mmol) over 10 minutes and the reaction stirred at −78° C. for a further 30 minutes. The reaction is then cooled to −78° C. before the dropwise addition of trimethyl borate (1.64 ml, 14.6 mmol) over 5 minutes. The reaction is stirred at −78° C. for 30 minutes, then allowed to warm to room temperature and stirred for a further 60 minutes. Palladium acetate (68 mg, 0.3 mmol), triphenylphosphine (314 mg, 1.2 mmol) and 4-chloro-iodobenzene (4.9 g, 12.15 mmol) is then added to the reaction, followed by THF (50 ml) and 1N sodium carbonate solution (20 ml) and the reaction is heated to reflux for 3 hours. The cooled reaction mixture is partitioned between ether (250 ml) and water (300 ml). The organic layer is separated, dried over magnesium sulphate, filtered and evaporated under reduced pressure. The residue is therefore purified by flash chromatography on silica gel to give 3-bromo-5-(4-chlorophenyl)-2-ethyl-thiophene as a white solid (2.75 g).

Fuente