(b) Synthesis of methyl 2-cyano-5-fluorobenzoate; Methyl 2-bromo-5-fluorobenzoate (3.0 g, 12.87 mmol; see step (a) above) was dissolved in anhydrous DMF (18 mL). Subsequently, degassing was carried out by passing N2 gas into the solution for 5 min. The reaction mixture was again degassed by adding cuprous(I) cyanide (2.3 g, 25.74 mmol) and then reacted under reflux conditions for 90 min. After completion of the reaction, 10% aqueous NaCN was added and the mixture was extracted with dichloromethane (DCM). The DCM phase was dried by a phase separator and the solvent was subsequently removed under vacuum. The crude product was dissolved in toluene and washed once with deionized water. The organic phase was dried with anhydrous magnesium sulfate (MgSO4) and filtered. Finally, the solvent was removed under vacuum to afford the crude methyl 2-cyano-5-fluorobenzoate (77% yield), which could be used in subsequent steps without further purification.1H NMR (500 MHz, CDCl3) δ 4.04 (s, 3H), 7.38 (dt, 1H), 7.82-7.87 (m, 2H).
