Br[C:2]1[C:11]([CH3:12])=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([CH3:13])=[N:9]2)=[CH:4][CH:3]=1.C([O:16][C:17](=[O:21])C([O-])=O)C.[K+].[OH-].[Na+]>CN1C(=O)CCC1.O.C(O)(C(F)(F)F)=O.C(O)(C(F)(F)F)=O.[Pd]>[CH3:13][C:8]1[CH:7]=[CH:6][C:5]2[C:10](=[C:11]([CH3:12])[C:2]([C:17]([OH:21])=[O:16])=[CH:3][CH:4]=2)[N:9]=1A 250 mL round-bottomed flask was charged with 7-bromo-2,8-dimethylquinoline (2.0 g, 8.47 mmol), potassium 2-ethoxy-2-oxoacetate (1.98 g, 12.7 mmol) and dcpp-2HBF4 (0.311 g, 0.508 mmol) in anhydrous NMP (28 mL) and nitrogen was bubbled into the mixture for 10 minutes, followed by the addition of Pd(TFA)2 (0.085 g, 0.254 mmol). The mixture was heated at 150° C. in an oil bath under a nitrogen atmosphere for 18 hours. The reaction mixture was cooled to ambient temperature and treated with a 2N NaOH solution (20 mL), and the mixture stirred at ambient temperature for 18 hours. The mixture was diluted with water (100 mL) and washed with ethyl acetate (180 mL). The aqueous layer was adjusted to pH 3 with 6N HCl and extracted with a 10% IPA-ethyl acetate solution. The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by reverse phase chromatography (Biotage SP4, 40M, C-18; 0-40% MeCN—H2O) to afford 2,8-dimethylquinoline-7-carboxylic acid (0.921 g, 54% yield).
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