Lithium hydroxide, monohydrate → (S)-6-(((3-Fluoropyridin-2-yl)(4-(trifluoromethoxy)phenyl)-methyl)carbamoyl)nicotinic Acid

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To a 150 mL round bottom flask containing (S)-methyl 6-(((3-fluoro-pyridin-2-yl)(4-(trifluoromethoxy)phenyl)methyl)carbamoyl)nicotinate (250 mg, 0.556 mmol) (prepared using the general coupling procedure Table 2 with Intermediate 1 and 5-((methylperoxy)carbonyl)picolinic acid) were added THF (6 mL) and H2O (2 mL). The resulting mixture was stirred at 23° C. for 2 min. At this time, lithium hydroxide monohydrate (61.8 μL, 2.23 mmol) was added and the reaction was stirred for 3 h. The bulk of the solvent was evaporated to give a foamy solid that oiled out. The residue was dissolved in AcOH (8 mL). The solution was purified by reverse phase HPLC and the product-containing fractions concentrated to give the title compound as a white solid. 1H NMR (300 MHz, CDCl3) δ ppm 9.65 (d, J=7.3 Hz, 1H), 9.21 (s, 1H), 8.61 (d, J=4.1 Hz, 1H), 8.42 (d, J=7.3 Hz, 1H), 8.24 (d, J=8.0 Hz, 1H), 7.63-7.42 (m, 3H), 7.39 (dd, J=4.2, 8.3 Hz, 1H), 7.20 (d, J=7.9 Hz, 2H), 6.74 (d, J=6.7 Hz, 1H). MS (ESI pos. ion) m/z: 436.2 (M+H).

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