Reaktion #1447101

Reaktionsgleichung

ethyl (4-ethyl-phenyl)-acetate

1-bromo-4-cyano-3,5-difluoro-benzene

hydrochloric acid

KOtBu

→

1-Bromo-4-cyano-3-fluoro-5-(4-ethyl-benzyl)-benzene

Lösungsmittel

NMP

NMP

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONcharged with a stir bar
2. 2
   Sonstigemaintains below 10° C
3. 3
   Extraktionextracted with ethyl acetate
4. 4
   TrocknenThe combined extracts are dried (Na2SO4)
5. 5
   Sonstigethe solvent is evaporated
6. 6
   workup.DISSOLUTIONThe residue is dissolved in THF (20 mL)
7. 7
   workup.ADDITIONtreated with 1M aqueous NaOH solution (80 mL)
8. 8
   workup.STIRRINGAfter stirring overnight at room temperature
9. 9
   Extraktionextracted with ethyl acetate
10. 10
    Trocknendried (Na2SO4)
11. 11
    Sonstigethe solvent is evaporated
12. 12
    workup.DISSOLUTIONThe residue is dissolved in DMF (25 mL)
13. 13
    workup.ADDITIONK2CO3 (5.5 g) is added
14. 14
    workup.STIRRINGThe resulting mixture is stirred at 100° C. for 1 h
15. 15
    TemperaturAfter cooling to room temperature
16. 16
    Extraktionthe resultant mixture is extracted with ethyl acetate
17. 17
    TrocknenThe combined organic extracts are dried (MgSO4)
18. 18
    Sonstigethe solvent is evaporated
19. 19
    SonstigeThe residue is purified by chromatography on silica gel (cyclohexane/ethyl acetate 1:0->1:1)

Vorschrift

KOtBu (6.7 g) is added to a flask charged with a stir bar and dry NMP (30 mL) and chilled to −10° C. under argon atmosphere. A solution of ethyl (4-ethyl-phenyl)-acetate (5.6 g) and 1-bromo-4-cyano-3,5-difluoro-benzene (6.4 g) in NMP (20 mL) is added at such a rate that the solution temperature maintains below 10° C. After stirring for 1 hour at 10° C., the solution is neutralized with 1 M aqueous hydrochloric acid and extracted with ethyl acetate. The combined extracts are dried (Na2SO4) and the solvent is evaporated. The residue is dissolved in THF (20 mL) and treated with 1M aqueous NaOH solution (80 mL). After stirring overnight at room temperature, the solution is acidified with 4 M HCl solution and extracted with ethyl acetate. The organic extracts are combined and dried (Na2SO4) and the solvent is evaporated. The residue is dissolved in DMF (25 mL) and K2CO3 (5.5 g) is added. The resulting mixture is stirred at 100° C. for 1 h. After cooling to room temperature, the mixture is neutralized with 1 M aqueous hydrochloric acid and the resultant mixture is extracted with ethyl acetate. The combined organic extracts are dried (MgSO4) and the solvent is evaporated. The residue is purified by chromatography on silica gel (cyclohexane/ethyl acetate 1:0->1:1).

Quelle