反应详情

温度

5 °C

A solution of 2,5-dibromo-6-picoline (30.6 kg, 122 mol, 1.00 eq) in toluene (154.2 kg) was dried by vacuum distillation at 40° C./75 mmHg to remove 105.7 kg of distillate to produce a solution containing 40 ppm water. This was mixed with 25 weight % sodium methoxide in methanol (124.1 kg, 574 mol, 4.71 eq) and the mixture was heated at 65–75° C. for 6 hours until reaction completion, (HPLC analysis indicated 1.6 area % starting material remained). The mixture was cooled to 5° C. and water (98 L) was charged to the mixture followed by t-butylmethylether (97 kg). The layers were separated and the organic phase washed twice with 5% brine (139 kg) and once with 20% brine (165 kg). The organic phase was clarified by filtration and 51 kg was removed by vacuum distillation at 40° C. to produce a 2-methoxy-5-bromo-6-picoline solution (58.4 kg) of 40.6 wt % purity (96% yield). Part of this was purified by distillation for the purposes of recording the 13C NMR spectrum: 13C NMR (400 MHz, CDCl3) δ 162.4, 154.4, 142.0, 111.8, 109.5, 53.6, 24.6.

1. customto remove 105.7 kg of distillate
2. customto produce a solution
3. temperaturethe mixture was heated at 65–75° C. for 6 hours until reaction completion, (HPLC analysis indicated 1.6 area % starting material remained)
4. customThe layers were separated
5. washthe organic phase washed twice with 5% brine (139 kg) and once with 20% brine (165 kg)
6. filtrationThe organic phase was clarified by filtration and 51 kg
7. customwas removed by vacuum distillation at 40° C.