[OH:1][C:2]1[CH:3]=[C:4]([CH3:10])[C:5](C#N)=[N:6][CH:7]=1.[C:11](=[O:14])([O-])[O-:12].[Cs+].[Cs+].FC(F)(F)S(O[CH2:23][C:24]([F:27])([F:26])[F:25])(=O)=O>CN(C=O)C.O.CCOC(C)=O>[CH3:10][C:4]1[C:5]([C:11]([OH:12])=[O:14])=[N:6][CH:7]=[C:2]([O:1][CH2:23][C:24]([F:27])([F:26])[F:25])[CH:3]=1To a solution of 5-hydroxy-3-methylpicolinonitrile (0.487 g, 3.63 mmol) in DMF (5 mL) were added cesium carbonate (1.538 g, 4.72 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (1.011 ml, 4.36 mmol) and the resulting suspension was stirred at rt overnight. The reaction was diluted with water and EtOAc. The organic layer was washed with 1M LiCl solution and brine before drying over magnesium sulfate and concentrating under reduced pressure. The material was taken up in EtOH (20 mL) and NaOH, 1.0M aq (10.89 ml, 10.89 mmol) was added. The reaction was heated to 80° C. and stirred for 6 hours. The reaction was heated to reflux and stirred overnight. The reaction was continued at reflux for a total of 4 days. The reaction was cooled to rt and diluted with ether and water. The organic layer was washed with additional water and the combined aqueous layers were acidified to pH=1 (pH paper) by the addition of 1M HCl. The aqueous layer was extracted with DCM (2×) and the combined organics were brined, dried over magnesium sulfate and concentrated under reduced pressure to afford 3-methyl-5-(2,2,2-trifluoroethoxy)picolinic acid (0.754 g, 3.21 mmol, 88% yield). LC/MS (ESI+) m/z=236 (M+H).
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