[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[C:8](Br)[C:7]([F:11])=[CH:6][C:5]=1[O:12][CH3:13].[C:15]([Cu])#[N:16].[Li+].[Cl-].Cl>CN(C=O)C.O.O.O.O.O.O.[Fe](Cl)(Cl)Cl.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[C:8]([C:15]#[N:16])[C:7]([F:11])=[CH:6][C:5]=1[O:12][CH3:13]
A stirring solution of 5-bromo-4-fluoro-2-methoxy-benzoic acid methyl ester (5.0 g, 10.0 mmol) in DMF (38 mL, 0.5 M) was treated with CuCN (3.92 g, 43.7 mmol). Equipped with a reflux condenser, the mixture was heated at 150° C. for 24 hours. After cooling, the reaction was poured into a 2 L erlenmeyer flask. Ethyl acetate (400 mL), saturated aq LiCl (100 mL), 1N HCl (100 mL)), 11 g of iron (III) chloride hexahydrate, and 15 mL of concd HCl was added to the solution. This green mixture was heated at 70° C. for 2 h (or until emulsion dissapated). After cooling to room temperature, the mixture was poured into a seperatory funnel and extracted with ethyl acetate (600 mL total). The combined organics were washed with 1N HCl (200 mL), saturated aq LiCl (2×200 mL) and saturated aq NaCl (100 mL). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification by MPLC (10-100% ethyl acetate in heptane, 23 mL/min, 75 min) provided 5-cyano-4-fluoro-2-methoxy-benzoic acid methyl ester (2.98 g, 75%) as a white crystalline solid: 1H NMR (CDCl3, 300 MHz)δ 8.15 (d, J=7.5 Hz, 1H), 6.80 (d, J=11.1 Hz, 1H), 3.97 (s, 3H), 3.90 (s, 3H).
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