Reacción #1598660

Ecuación de reacción

4-Ethoxy-2,3-difluorophenol

tripotassium phosphate

compound ( 5 )

4′-chloromethyl-4-ethoxy-2,3-difluoro-biphenyl

→

4-ethoxy-2,3-difluoro-4′-(4-ethoxy-2,3-difluorophenoxymethyl)-1,1′-biphenyl

Rendimiento 74.0%

Disolventes

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrowas continued at 70° C
2. 2
   OtroAfter the reaction mixture obtained
3. 3
   Otroseparated from the solid by filtration, toluene (100 ml) and water (100 ml)
4. 4
   workup.ADDITIONwere added
5. 5
   workup.ADDITIONmixed
6. 6
   Otrohad separated into two phases of organic and aqueous phases
7. 7
   ExtracciónThe extraction into an organic phase
8. 8
   OtroThe organic phase obtained
9. 9
   Lavadowas washed with brine
10. 10
    Secadodried over anhydrous magnesium sulfate
11. 11
    workup.DISTILLATIONThen, the solvent was distilled off
12. 12
    Otrothe residue obtained
13. 13
    Otrowas purified by means of column chromatography (silica gel; heptane: toluene=1:2 by volume)
14. 14
    OtroThe product was further purified by means of recrystallization from a mixed solvent of Solmix A-11 and heptane (Solmix A-11: heptane=1:2 by volume)
15. 15
    Otrodried

Procedimiento

4-Ethoxy-2,3-difluorophenol (6) (1.5 g) and tripotassium phosphate (K3PO4) (7.5 g) were added to DMF (100 ml) under a nitrogen atmosphere, and the stirring was continued at 70° C. The compound (5) (2.0 g) was added thereto and the stirring was continued at 70° C. for 7 hours. After the reaction mixture obtained had been cooled to 30° C. and then separated from the solid by filtration, toluene (100 ml) and water (100 ml) were added thereto and mixed. The mixture was then allowed to stand until it had separated into two phases of organic and aqueous phases. The extraction into an organic phase was carried out. The organic phase obtained was washed with brine and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off, and the residue obtained was purified by means of column chromatography (silica gel; heptane: toluene=1:2 by volume). The product was further purified by means of recrystallization from a mixed solvent of Solmix A-11 and heptane (Solmix A-11: heptane=1:2 by volume) and dried, giving 2.2 g of 4-ethoxy-2,3-difluoro-4′-(4-ethoxy-2,3-difluorophenoxymethyl)-1,1′-biphenyl (No. 678). The yield based on the compound (5) was 74.0%.

Fuente