Reacción #420030

Ecuación de reacción

trimethylacetic acid

6-methoxybenzo[b]thiophene

1-bromo-4-fluorobenzene

potassium carbonate

→

2-(4-fluorophenyl)-6-methoxybenzo[b]thiophene

Rendimiento 54.1%

Disolventes

DMA

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe microwave vial was sealed
2. 2
   Otropurged with nitrogen
3. 3
   Otroirradiation at 150° C. for 2 h
4. 4
   workup.ADDITIONUpon completion the reaction mixture was diluted with water
5. 5
   Extracciónextracted with EtOAc
6. 6
   LavadoThe combined organic layers were then washed with brine
7. 7
   Secadodried over anhydrous MgSO4
8. 8
   Filtraciónfiltered
9. 9
   Concentraciónconcentrated in vacuo
10. 10
    OtroThe resulting crude material was purified via trituration 2× with heptane
11. 11
    Otrothe remaining triturate (
12. 12
    workup.ADDITIONcontaining some product)
13. 13
    Concentraciónwas concentrated
14. 14
    Otropurified by column chromatography (SiO2, 0-30% EtOAc/Heptane)

Procedimiento

To a 5 mL microwave vial was added a solution of 6-methoxybenzo[b]thiophene (400 mg, 2.44 mmol) in anhydrous DMA (3 mL) followed by 1-bromo-4-fluorobenzene (448 mg, 2.56 mmol), chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′,4′,6′-tri-1-propyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) (BrettPhos palladacycle 1st generation, 97 mg, 0.12 mmol), trimethylacetic acid (746 mg, 7.31 mmol) and potassium carbonate (1.01 g, 7.31 mmol). The microwave vial was sealed, purged with nitrogen and subjected to microwave irradiation at 150° C. for 2 h. Upon completion the reaction mixture was diluted with water and extracted with EtOAc. The combined organic layers were then washed with brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. The resulting crude material was purified via trituration 2× with heptane and the remaining triturate (containing some product) was concentrated and purified by column chromatography (SiO2, 0-30% EtOAc/Heptane) to afford 2-(4-fluorophenyl)-6-methoxybenzo[b]thiophene (340 mg, 1.32 mmol, 54% yield). 1H NMR (400 MHz, (CD3)2SO) δ ppm=3.79-3.93 (m, 3H), 7.01 (dd, J=8.59, 2.53 Hz, 1H), 7.24-7.42 (m, 2H), 7.56 (d, J=2.53 Hz, 1H), 7.67-7.86 (m, 4H). LC/MS (m/z, MH+): 258.8.

Fuente