Lithium Hydroxide → 5-Chloro-2-(4-fluorophenoxy)nicotinic acid

Ethyl 2,5-dichloronicotinate (2.50 g) was combined with 4-fluorophenol (1.49 g) in a sealable tube containing anhydrous 1,4-dioxane (7 mL). Anhydrous cesium carbonate (4.52 g) was added, and the reaction mixture immersed in a heated oil bath (105° C.) overnight. After cooling to ambient temperature, the resulting suspension was filtered and the solids washed with 1,4-dioxane (2×10 mL). The filtrate was collected and concentrated in vacuo to yield a crude solid (3.89 g). Tetrahydrofuran (12 mL) was added to the crude solid, followed by water (20 mL), and finely ground lithium hydroxide (1.36 g). The solution was allowed to stir 5 hours at room temperature. The organics were then removed in vacuo and the pH of the solution was then adjusted from 14 to 2 with 3N aq. hydrochloric acid. The resulting mixture was then extracted with ethyl acetate (5×50 mL). The combined organics were dried over magnesium sulfate, filtered and concentrated to dryness in vacuo to yield the crude title compound (2.71 g).

1. customthe reaction mixture immersed in a heated oil bath
2. custom(105° C.) overnight
3. filtrationthe resulting suspension was filtered
4. washthe solids washed with 1,4-dioxane (2×10 mL)
5. customThe filtrate was collected
6. concentrationconcentrated in vacuo
7. customto yield a crude solid (3.89 g)
8. customThe organics were then removed in vacuo
9. extractionThe resulting mixture was then extracted with ethyl acetate (5×50 mL)
10. dry with materialThe combined organics were dried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated to dryness in vacuo

ORD record

ord-42c86c55eb014047b580e02e68d5d00f

Source dataset

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07250518B2