Water → 6-Fluoropyridine-2-carboxylic acid

Temperature

100 °C

To a heterogeneous solution of 2-fluoro-6-methyl-pyridine (9.65 g, 86.8 mmol) in water (400 mL) was added potassium permanganate (31.6 g, 200 mmol), and the reaction was heated to approximately 100° C. After 30 minutes, additional potassium permanganate (16.5 g, 104 mmol) was added, and the reaction heated at 100° C. overnight. The reaction was filtered through celite to remove manganese salts. The mother liquor was washed with ethyl ether (200 mL×3), neutralized to pH 7, and concentrated down to approximately 100 mL total volume. The aqueous solution was acidified to pH 2 with concentrated HCl and extracted with ethyl acetate, followed by 20% i-PrOH/CHCl3 (×3). The combined organic layers were dried over MgSO4 and concentrated. The solids were suspended in chloroform, sonicated, then filtered to remove remaining side products. The mother liquor was concentrated to give 5.47 g as a white crystalline solid, 45% yield. 1H NMR: consistent with structure. MS (ion spray) 140 (M−).

1. temperaturethe reaction heated at 100° C. overnight
2. filtrationThe reaction was filtered through celite
3. customto remove manganese salts
4. washThe mother liquor was washed with ethyl ether (200 mL×3)
5. concentrationconcentrated down to approximately 100 mL total volume
6. extractionextracted with ethyl acetate
7. dry with materialThe combined organic layers were dried over MgSO4
8. concentrationconcentrated
9. customsonicated
10. filtrationfiltered
11. customto remove
12. concentrationThe mother liquor was concentrated
13. customto give 5.47 g as a white crystalline solid, 45% yield

ORD record

ord-a5c68623ed1b4ed084d1a993ff6dadcf

Source dataset

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06743794B2