To a mixture of the above compound (S1) (130 mg, 0.393 mmol) and Pd(dppf)Cl2-CH2Cl2 adduct (32.1 mg, 0.039 mmol) and Cs2CO3 (384 mg, 1.178 mmol) in a microwave tube was add a solution of 5-(chloromethyl)-2-methoxypyridine (124 mg, 0.785 mmol) in THF (3 mL) followed by water (0.3 mL). The mixture was heated at 100° C. for 1 h. LC-MS indicated the product (S2) existed as a mixture of both desired ester (ES-MS [M+1]+: 327.2) and hydrolyzed acid (ES-MS [M+1]+: 313.2). The mixture was transferred to a 100 mL round-bottom flask followed by adding MeOH (11 mL) and NaOH (1 N in H2O, 4.5 mL). The reaction was stirred at room temperature for 1 h to allow the complete conversion of the remaining ester to the acid. The solvents were removed to provide crude 8-fluoro-4-[(6-methoxypyridin-3-yl)methyl]quinoline-2-carboxylic acid (S3). ES-MS [M+1]+: 313.2.
