Example 58 Synthesis of 4-((5-fluoro-2-(4-fluorophenyl)pyridin-3-yl]methyl}amino)methylbenzoic acid Procedure 1. Preparation of methyl 5-fluoro-2-(4-fluorophenyl)nicotinate: 2-chloro-5-fluoronicotinic acid (1.00 g, 5.70 mmol) was dissolved in a mixture of solvents of methanol (4 mL) and dichloromethane (14 mL) at 0 °C, and slowly added to a 2M hexane solution of trimethylsilylated diazomethane (5.70 mL, 11.4 mmol). The reaction mixture was stirred at 0 °C for 1 hour. Upon completion of the reaction, the reaction was quenched with acetic acid and the solvent was removed by concentration under reduced pressure. The residue was purified by fast column chromatography on silica gel using hexane/ethyl acetate (10:1, v/v) as eluent to afford 0.78 g (72% yield) of methyl 2-chloro-5-fluoronicotinate as a colorless oil. The product was characterized by 1H-NMR (CDCl3): δ 8.41 (1H, d, J=3.1 Hz), 7.93 (1H, dd, J=7.6,3.1 Hz), 3.98 (3H, s).
