反应详情

温度

15 °C

To a cold suspension (0-10° C.) of 6-[2-(2,4-difluorophenyl)ethynyl]-3-nitro-pyridin-2-amine (500 g, 1.82 mol) in acetone (10 L), is added cold buffer [NaH2PO4 (0.8 M)/Na2HPO4 (0.8 M)=85/15 (V/V)] (pH=6.0; 0-10° C.; 10 L). The temperature is maintained at 15° C. Potassium permanganate (1035 g, 6.55 mol) is added portionwise (3 portions). The mixture is stirred for 4 h at 15° C. The pH is adjusted to pH=5.0 and the temperature is kept below 15° C. A 28% sodium thiosulfate solution (2054 mL, 3.64 mol) is added slowly, maintaining the temperature below 15° C. and the pH below 7.5. Brine (7.5 L) and a mixture of methyl tert-butyl ether (3.75 L) and ethyl acetate (3.75 L) are added to the suspension. The mixture is stirred for 15 min at 13° C. The two phases are separated and the aqueous brown suspension is extracted twice with methyl tert-butyl ether (3.5 L). The combined organic layers are collected and washed with brine (2×3 L), dried over Na2SO4, filtered, and the solvent is evaporated under reduced pressure to obtain the title compound as a yellow solid (375 g). The experiment is repeated under the same conditions twice more. The resulting batches are combined to afford 1080 g. LC-ES/MS m/z 308 (M+1).

1. customis kept below 15° C
2. temperaturemaintaining the temperature below 15° C.
3. additionare added to the suspension
4. stirringThe mixture is stirred for 15 min at 13° C
5. customThe two phases are separated
6. extractionthe aqueous brown suspension is extracted twice with methyl tert-butyl ether (3.5 L)
7. customThe combined organic layers are collected
8. washwashed with brine (2×3 L)
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. customthe solvent is evaporated under reduced pressure