Lithium Hydroxide → 2-(Benzo[1,3]dioxol-5-yloxy)-5-fluoro-nicotinic acid

Temperatur

100 °C

2-Chloro-5-fluoro-nicotinic acid (synthesized in accordance with the procedures described in European patent: EP 0634413 A1) was converted to the corresponding ethyl ester with anhydrous ethanol and excess thionyl chloride, then worked up in the usual manner. To 2-chloro-5-fluoro-nicotinic acid ethyl ester (5.0 g) in an oven-dried 250 mL flask was added cesium carbonate (9.60 g), sesamol (4.07 g), and 50 mL of anhydrous dioxane. The reaction was stirred overnight at 100° C. Lithium hydroxide (2.94 g) in 10 mL water was added, and the reaction was again allowed to stir overnight at 100° C. The dioxane was then evaporated under a nitrogen stream. The residue was then taken up in 50 mL water, acidified with conc. hydrochloric acid to pH=3, and extracted with ethyl acetate (3×100 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. The dried residue was washed with ethyl acetate (20 mL) and dried under high vacuum, giving the title compound (2.96 g).

1. stirringto stir overnight at 100° C
2. customThe dioxane was then evaporated under a nitrogen stream
3. extractionextracted with ethyl acetate (3×100 mL)
4. dry with materialThe combined organic extracts were dried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. washThe dried residue was washed with ethyl acetate (20 mL)
8. customdried under high vacuum

ORD-Eintrag

ord-5b620ec16e76469fb59f266b6b9a423d

Quelldatensatz

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07183293B2