反応 #1447101

反応方程式

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

溶媒

NMP

NMP

反応条件

後処理

1. 1
   workup.ADDITIONcharged with a stir bar
2. 2
   その他maintains below 10° C
3. 3
   抽出extracted with ethyl acetate
4. 4
   乾燥The combined extracts are dried (Na2SO4)
5. 5
   その他the 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
   抽出extracted with ethyl acetate
10. 10
    乾燥dried (Na2SO4)
11. 11
    その他the 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
    温度After cooling to room temperature
16. 16
    抽出the resultant mixture is extracted with ethyl acetate
17. 17
    乾燥The combined organic extracts are dried (MgSO4)
18. 18
    その他the solvent is evaporated
19. 19
    その他The residue is purified by chromatography on silica gel (cyclohexane/ethyl acetate 1:0->1:1)

実験手順

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).

出典