Potassium Carbonate → HCID 58243611, compound

Temperature

80 °C

4-chloro-2,6-difluorophenol (5.11 g) was dissolved in DMF (100 ml), ethyl 2-bromo-2-methylpropanoate (14 ml) and potassium carbonate (6.44 g) were added thereto, followed by stirring at 80° C. for 3 hours. The reaction solution was cooled to room temperature, water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with a 1M aqueous sodium hydroxide solution and then 1M hydrochloric acid in this order and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=19:1) to obtain a colorless oily product. The oily product thus obtained was dissolved in ethanol (150 ml), a 1M aqueous sodium hydroxide solution (65 ml) was added thereto, followed by stirring at room temperature for one hour. The reaction solution was concentrated under reduced pressure and water was added to the resulting residue, followed by washing with ethyl acetate. 1M hydrochloric acid was added to the aqueous layer, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to obtain a colorless oily product. Acetonitrile (75 ml), WSC•monohydrochloride (7.18 g) and HOBt (5.04 g) were added to the oily product thus obtained, followed by stirring at room temperature for one hour. The resulting reaction solution was added to a mixed solution of hydrazine monohydrate (7.55 ml) and acetonitrile (75 ml), followed by stirring at room temperature overnight. The reaction solution was concentrated under reduced pressure, water was added thereto, followed by extraction with chloroform. The organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine. After drying over anhydrous magnesium sulfate and aeration, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate). The resulting residue was purified by silica gel column chromatography (chloroform:methanol=100:1) to obtain 2-(4-chloro-2,6-difluorophenoxy)-2-methylpropanohydrazide (5.69 g) as a pink oily product.

1. temperatureThe reaction solution was cooled to room temperature
2. extractionfollowed by extraction with ethyl acetate
3. washThe organic layer was washed with a 1M aqueous sodium hydroxide solution
4. dry with material1M hydrochloric acid in this order and dried over anhydrous magnesium sulfate
5. customthe solvent was evaporated under reduced pressure
6. customThe resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=19:1)
7. customto obtain a colorless oily product
8. customThe oily product thus obtained
9. stirringby stirring at room temperature for one hour
10. concentrationThe reaction solution was concentrated under reduced pressure and water
11. additionwas added to the resulting residue
12. washby washing with ethyl acetate
13. addition1M hydrochloric acid was added to the aqueous layer
14. extractionfollowed by extraction with ethyl acetate
15. washThe organic layer was washed with saturated brine
16. dry with materialdried over anhydrous magnesium sulfate
17. customThe solvent was evaporated under reduced pressure
18. customto obtain a colorless oily product
19. customthus obtained
20. stirringby stirring at room temperature for one hour
21. customThe resulting reaction solution
22. stirringby stirring at room temperature overnight
23. concentrationThe reaction solution was concentrated under reduced pressure, water
24. additionwas added
25. extractionfollowed by extraction with chloroform
26. washThe organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine
27. dry with materialAfter drying over anhydrous magnesium sulfate and aeration
28. customthe solvent was evaporated under reduced pressure
29. customThe residue was purified by silica gel column chromatography (ethyl acetate)
30. customThe resulting residue was purified by silica gel column chromatography (chloroform:methanol=100:1)

ORD record

ord-c2e83992111a4a39b41fb34eafaca83f

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08377923B2