反应详情

温度

150 °C

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, 0.75%) as a white crystalline solid: 1H NMR (CDCl3, 300 MHz) δ 8.15 (d, J=7.5 Hz, 1 H), 6.80 (d, J=11.1 Hz, 1 H), 3.97 (s, 3 H), 3.90 (s, 3 H).

1. customEquipped with a reflux condenser
2. temperatureAfter cooling
3. additionthe reaction was poured into a 2 L erlenmeyer flask
4. temperatureThis green mixture was heated at 70° C. for 2 h (or until emulsion dissapated)
5. temperatureAfter cooling to room temperature
6. additionthe mixture was poured into a seperatory funnel
7. extractionextracted with ethyl acetate (600 mL total)
8. washThe combined organics were washed with 1N HCl (200 mL), saturated aq LiCl (2×200 mL) and saturated aq NaCl (100 mL)
9. dry with materialThe organic layer was dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customPurification by MPLC (10–100% ethyl acetate in heptane, 23 mL/min, 75 min)