Hydrochloric Acid → 5-(Difluoromethoxy)picolinic acid

A solution of C7 (17 g, 84 mmol) in tetrahydrofuran (100 mL) and water (50 mL) was cooled to 0° C. and treated with lithium hydroxide (6.0 g, 250 mmol). After the reaction mixture had stirred at room temperature for 2 hours, it was acidified to a pH of 3 with 1 M aqueous hydrochloric acid. The aqueous layer was extracted with ethyl acetate (3×100 mL), and the combined organic layers were washed with saturated aqueous sodium chloride solution (100 mL), dried, filtered, and concentrated under reduced pressure to provide the product as a white solid. Yield: 13 g, 69 mmol, 82%. LCMS m/z 189.8 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.52 (d, J=2.4 Hz, 1H), 8.29 (d, J=8.5 Hz, 1H), 7.73 (dd, J=8.6, 2.4 Hz, 1H), 6.68 (t, JHF=71.5 Hz, 1H).

1. extractionThe aqueous layer was extracted with ethyl acetate (3×100 mL)
2. washthe combined organic layers were washed with saturated aqueous sodium chloride solution (100 mL)
3. customdried
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure

ORD record

ord-f27e41826e9e4a7d890eca57ca64f759

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09315520B2