2,5-Dichlorophenol → 4-(2,5-Dichloro-phenoxy)-nicotinic acid

温度

120 °C

To a suspension of 10 g (63.47 mmol) 4-chloronicotinic acid (commercially available; CAS RN 10177-29-4) and 11.38 g (69.81 mmol) 2,5-dichlorophenol (commercially available CAS RN 583-78-8) in 50 mL dry N,N-dimethylformamide were added 17.55 g (126.94 mmol) potassium carbonate, 1.21 g (6.35 mmol) copper(I)iodide and 1.21 g (19.04 mmol) copper nanopowder. The green suspension was stirred at 120° C. (oil bath temperature) for 3 hours and then cooled down to 80° C. At that temperature, 400 mL water were added, the suspension was stirred at 80° C. for 5 min., filtered over Dicalite® speed plus (Acros) and the filter cake washed twice with 50 mL water. The resulting filtrate was extracted three times with ethyl acetate and then the pH was adjusted to 4-5 using 140 mL 1M aqueous hydrochloric acid. The resulting green, turbid solution was treated with ethyl acetate, stirred for 5 min. and filtered. The blue solid that had formed was filtered off and the layers of the filtrate were separated. The aqueous layer was saturated with solid sodium chloride and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. To the resulting solid 200 mL saturated aqueous potassium carbonate solution and 200 mL ethyl acetate were added. The aqueous layer was extracted twice with 200 mL ethyl acetate and the pH was adjusted to 4 using 25% aqueous hydrochloric acid. The resulting suspension was extracted three times with ethyl acetate. The combined organic layers were washed three times with water and once with brine, dried over magnesium sulfate, filtered and evaporated to give the desired compound as a light brown solid (7.29 g, 40%). MS (ESI): m/z=281.8 [M−H]−.

1. temperaturecooled down to 80° C
2. stirringthe suspension was stirred at 80° C. for 5 min.
3. filtrationfiltered over Dicalite® speed plus (Acros)
4. washthe filter cake washed twice with 50 mL water
5. extractionThe resulting filtrate was extracted three times with ethyl acetate
6. additionThe resulting green, turbid solution was treated with ethyl acetate
7. stirringstirred for 5 min.
8. filtrationfiltered
9. customThe blue solid that had formed
10. filtrationwas filtered off
11. customthe layers of the filtrate were separated
12. extractionextracted three times with ethyl acetate
13. washThe combined organic layers were washed with brine
14. dry with materialdried over magnesium sulfate
15. filtrationfiltered
16. customevaporated
17. additionTo the resulting solid 200 mL saturated aqueous potassium carbonate solution and 200 mL ethyl acetate were added
18. extractionThe aqueous layer was extracted twice with 200 mL ethyl acetate
19. extractionThe resulting suspension was extracted three times with ethyl acetate
20. washThe combined organic layers were washed three times with water
21. dry with materialonce with brine, dried over magnesium sulfate
22. filtrationfiltered
23. customevaporated

ORDレコード

ord-94fed5cac8894db99617fea856a7e7c7

出典データセット

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08729091B2