[NH2:1][C:2]1[C:7]([F:8])=[C:6](F)[N:5]=[C:4]([C:10]([O:12][CH:13]([CH3:15])[CH3:14])=[O:11])[CH:3]=1.C([O-])(O)=O.[Na+].[ClH:21]>CCOC(C)=O>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([Cl:21])[N:5]=[C:4]([C:10]([O:12][CH:13]([CH3:15])[CH3:14])=[O:11])[CH:3]=1Propan-2-yl 4-amino-5,6-difluoropicolinate (4.25 g, 19.7 mmol) was dissolved in HCl (4 M in dioxane; 65 mL) in a 100 mL Hastalloy stirred Parr reactor. The reactor was heated at 100° C. for 2 h. Upon standing at room temperature overnight, a yellow crystalline solid formed. This solid was not soluble in EtOAc but did dissolve upon shaking with satd aq NaHCO3 (500 mL) and EtOAc (300 mL). The aqueous layer was extracted with EtOAc (2×250 mL). The combined organic extracts were washed with H2O (5×50 mL) and then with satd aq NaCl. The extracts were dried (MgSO4) and concentrated under vacuum to provide an off-white solid. The crude product was purified by column chromatography (120 g silica column; 0-100% hexane-EtOAc gradient) to give a white solid (2.11 g, 46%): mp 190.7-192.4° C.; 1H NMR (400 MHz, DMSO-d6) δ 7.543 (d, JF-H=5.7 Hz, 1H), 6.91 (br s, 2H, NH2), 5.09 (septet, J=6 Hz, 1H, CHMe2), 1.29 (d, J=6 Hz, 6H, CHMe2); 13C{1H} NMR (101 MHz, DMSO-d6) δ 162.8 (CO2R), 144.8 (d, JF-C=12 Hz, C2/C4), 143.4 (d, JF-C=254 Hz, C5), 142.7 (d, JF-C=4.8 Hz, C2/C4), 136.5 (d, JF-C=17 Hz, C6), 112.8 (d, JF-C=5 Hz, C3), 68.9 (CHMe2), 21.6 (Me); 19F NMR (376 MHz, DMSO-d6) δ −141.0 (d, JF-H=6 Hz). Anal. Calcd for C9H10ClFN2O2: C, 46.47; H, 4.33; N, 13.75. Found: C, 46.50; H, 4.33; N, 11.96.
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