反应详情

A solution of 6-amino-3-bromo-2-methylpyridine (239 g, 1278 mmol) in concentrated HCl (1.0 L) was cooled to −5° C. A solution of sodium nitrite (238 g, 3450 mmol) in water (1.0 L) was added dropwise over 1 hour while maintaining the temperature of the reaction between −5 and 5° C. After the addition was complete, the reaction was stirred for 1 hour, and then the cooling bath was removed and the reaction was warmed to r.t. and stirred for 16 hours. The reaction was then poured onto ice and 5N NaOH (1.7 L) was added to adjust the pH of the solution to 13. The mixture was extracted 3 times with EtOAc (3 L and 2×2 L). The combined organic layers were dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel with 100% methylene chloride afforded 3-bromo-6-chloro-2-methylpyridine. 1H NMR (CDCl3, 500 MHz) δ 7.76 (d, J=8.2 Hz, 1H), 7.07 (d, J=8.1 Hz, 1H), 2.66 (s, 3H).

1. temperaturewhile maintaining
2. customthe temperature of the reaction between −5 and 5° C
3. additionAfter the addition
4. customthe cooling bath was removed
5. stirringstirred for 16 hours
6. additionThe reaction was then poured onto ice and 5N NaOH (1.7 L)
7. additionwas added
8. extractionThe mixture was extracted 3 times with EtOAc (3 L and 2×2 L)
9. dry with materialThe combined organic layers were dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated
12. customPurification of the residue by flash chromatography on silica gel with 100% methylene chloride