反应详情

温度

120 °C

To solution of methyl 5-chloro-2,4-difluorobenzoate (25.9 mg, 0.125 mmol) and 3-ethoxyphenol (17.3 mg, 0.125 mmol) in dimethyl formamide (0.5 mL) was added cesium carbonate (82 mg, 0.25 mmol), the mixture was shaken at 120° C. for 16 hours, filtered and evaporated in vacuo. Water (1 mL) was added and extracted with ethyl acetate (3×1 mL), the combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The residue was dissolved in THF (0.7 mL) and to this solution was added a 1M aqueous solution of lithium hydroxide (0.7 mL) and the mixture was shaken at 30° C. for 16 hours. The reaction mixture was evaporated in vacuo, a 1M aqueous solution of hydrochloric acid (0.7 mL) was added and extracted with ethyl acetate (3×1 mL). The combined organic layers were dried over anhydrous sodium sulphate, filtered and evaporated in vacuo. To this residue was added methanesulfonamide (28.6 mg, 0.300 mmol) and a solution of 4-dimethylaminopyridine (24.4 mg, 0.200 mmol) and EDCl (38.3 mg, 0.200 mmol) in dichloromethane (1 mL), the solution was shaken at 30° C. for 16 hours and evaporated in vacuo. The crude product was purified on a HPLC column (Sepax BR-C18 100*21.2 mm*5 μm, acetonitrile-water (0.1% trifluoroacetic acid) gradient to yield 6.2 mg (16 μmol) 5-chloro-4-(3-ethoxyphenoxy)-2-fluoro-N-(methylsulfonyl)benzamide.

1. filtrationfiltered
2. customevaporated in vacuo
3. additionWater (1 mL) was added
4. extractionextracted with ethyl acetate (3×1 mL)
5. dry with materialthe combined organic layers were dried over sodium sulphate
6. filtrationfiltered
7. customevaporated in vacuo
8. dissolutionThe residue was dissolved in THF (0.7 mL) and to this solution
9. additionwas added a 1M aqueous solution of lithium hydroxide (0.7 mL)
10. stirringthe mixture was shaken at 30° C. for 16 hours
11. customThe reaction mixture was evaporated in vacuo
12. additiona 1M aqueous solution of hydrochloric acid (0.7 mL) was added
13. extractionextracted with ethyl acetate (3×1 mL)
14. dry with materialThe combined organic layers were dried over anhydrous sodium sulphate
15. filtrationfiltered
16. customevaporated in vacuo
17. customevaporated in vacuo
18. customThe crude product was purified on a HPLC column (Sepax