Tetrahydrofuran → 6-(DifluoroMethyl)-2-pyridinecarboxylic Acid

To a solution of methyl 6-(difluoromethyl)pyridine-2-carboxylate (0.58 g, 3.1 mmol, from Step 1) in Water (22 mL) and Tetrahydrofuran (20 mL, 250 mmol) was added Lithium hydroxide, monohydrate (0.65 g, 15 mmol). The reaction was stirred for 2 hours. The basic mixture was extracted with ether, which was discarded. The mixture was then acidified by the addition of 1N HCl and the volume of solvent reduced in vacuo. The product was purified via preparative HPLC-MS (C18, eluting with a gradient of H2O/MeCN containing 0.1% TFA). The eluent containing the desired mass was evaporated by rotary evaporation to afford a solid product (0.35 g, 65%). 1H NMR (400 MHz, CD3OD): δ 8.27 (ddd, 1H), 8.17 (dd, 1H), 7.92 (dd, 1H), 6.78 (t, 1H); 1H NMR (400 MHz, CD3OD): δ−117.52 (d, 2F); LCMS (M+H)+: 173.9.

1. extractionThe basic mixture was extracted with ether, which
2. additionThe mixture was then acidified by the addition of 1N HCl
3. customThe product was purified via preparative HPLC-MS (C18
4. washeluting with a gradient of H2O/MeCN containing 0.1% TFA)
5. additionThe eluent containing the desired mass
6. customwas evaporated by rotary evaporation

ORD record

ord-b078d962073f43c88ed609df7611a296

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08933085B2