Tetrahydrofuran → 6-(DifluoroMethyl)-2-pyridinecarboxylic Acid
Reaction equation
[F:1][CH:2]([F:13])[C:3]1[N:8]=[C:7]([C:9]([O:11]C)=[O:10])[CH:6]=[CH:5][CH:4]=1.O1CCCC1.O.[OH-].[Li+]>O>[F:13][CH:2]([F:1])[C:3]1[N:8]=[C:7]([C:9]([OH:11])=[O:10])[CH:6]=[CH:5][CH:4]=1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
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.