反应详情

温度

10 °C

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).

1. additioncharged with a stir bar
2. custommaintains below 10° C
3. extractionextracted with ethyl acetate
4. dry with materialThe combined extracts are dried (Na2SO4)
5. customthe solvent is evaporated
6. dissolutionThe residue is dissolved in THF (20 mL)
7. additiontreated with 1M aqueous NaOH solution (80 mL)
8. stirringAfter stirring overnight at room temperature
9. extractionextracted with ethyl acetate
10. dry with materialdried (Na2SO4)
11. customthe solvent is evaporated
12. dissolutionThe residue is dissolved in DMF (25 mL)
13. additionK2CO3 (5.5 g) is added
14. stirringThe resulting mixture is stirred at 100° C. for 1 h
15. temperatureAfter cooling to room temperature
16. extractionthe resultant mixture is extracted with ethyl acetate
17. dry with materialThe combined organic extracts are dried (MgSO4)
18. customthe solvent is evaporated
19. customThe residue is purified by chromatography on silica gel (cyclohexane/ethyl acetate 1:0->1:1)