反应详情

1 g. (5.35 mmol.) of 2,6-dichloro-3-cyano-4-methylpyridine and approximately 40 ml. of t-butylamine (distilled from sodium hydride) were heated together in a reaction bomb at 200° C. for 5 hrs. Heating for an additional 4 hrs. at the same temperature produced no further change in the reaction mixture. The reaction mixture was allowed to stand overnight and was evaporated at reduced pressure to obtain a gummy solid. The gummy solid was partitioned between water containing a trace of sodium carbonate and chloroform, and the aqueous phase was re-extracted twice with chloroform. The three chloroform phases were combined, dried over anhydrous sodium sulfate and evaporated at reduced pressure. The residue was dissolved in 10 ml. of chloroform and diluted to 70 ml. with hexane. The small amount of crystals that formed were removed by filtration and the filtrate was applied to a column of 50 ml. of silica gel packed in 20% chloroform in hexane and eluted with the same solvent mixture. The first 130 ml. of eluate contained nothing, and the next 100 ml. of eluate were evaporated to obtain 6-t-butylamino-2-chloro-3-cyano-4-methylpyridine (0.49 g.), m.p. 109° C. The next fractions, containing the desired product, were combined and evaporated at reduced pressure and hexane was added. After evaporation of the hexane at reduced pressure, the residue was allowed to crystallize in the freezer to obtain the desired product (0.362 g.), m.p. 134°-138° C.

1. temperatureHeating for an additional 4 hrs
2. customat the same temperature produced no further change in the reaction mixture
3. customwas evaporated at reduced pressure
4. customto obtain a gummy solid
5. customThe gummy solid was partitioned between water containing a trace of sodium carbonate and chloroform
6. extractionthe aqueous phase was re-extracted twice with chloroform
7. dry with materialdried over anhydrous sodium sulfate
8. customevaporated at reduced pressure
9. dissolutionThe residue was dissolved in 10 ml
10. additionof chloroform and diluted to 70 ml
11. customThe small amount of crystals that formed
12. customwere removed by filtration
13. washeluted with the same solvent mixture
14. customof eluate were evaporated