反应详情

温度

5 °C

3-Amino-4-chlorobenzoic acid (18.72 g, 109.1 mmol), commercially available, was added to a mixture of water (200 mL) and 37% HCl (35 mL), and the resulting slurry was cooled to 5° C. A solution of NaNO2 (8.65 g, 125 mmol) in water (70 mL) was added dropwise, and the solution stirred at 5° C for 30 min. The solution was then added to a slurry consisting of water (400 mL), CuCN (9.85 g, 109 mmol),and KCN(12.06g, 185 mmol), while maintaining the temperature at5°-10° C. The mixture was stirred at 10° C. for another 30 min, and then heated to 80° C. for 1 hour. The reaction was cooled, and the pH adjusted to ~1 by addition of concentrated HCl. The solution was extracted with 5× CHCl3, and the combined extracts were rinsed with 1M HCl and brine, and dried over MgSO4. The solvent was removed in vacuo, and the crude product was recrystallized from CHCl3 /EtOAc to yield 15.9 g (80%) of the title compound. m.p. 180° C. 1H NMR (300 MHz, CDCl3) δ 10.55 (br s, 1H), 8.42 (d, 1H), 8.26 (dd, 1H), 7.68 (d, 1H). MS (DCI/NH3) m/e 213 (M+NH4)+.

1. additionThe solution was then added to a slurry
2. temperaturewhile maintaining the temperature at5°-10° C
3. stirringThe mixture was stirred at 10° C. for another 30 min
4. temperatureheated to 80° C. for 1 hour
5. temperatureThe reaction was cooled
6. extractionThe solution was extracted with 5× CHCl3
7. washthe combined extracts were rinsed with 1M HCl and brine
8. dry with materialdried over MgSO4
9. customThe solvent was removed in vacuo
10. customthe crude product was recrystallized from CHCl3 /EtOAc