反应详情

To a stirred solution of potassium tert-butoxide (53.6 g, 479 mmol) in anhydrous NMP (200 mL) under a nitrogen atmosphere at 80° C. was added a solution of 5-trifluoromethyl-3-((trimethylsilyl)ethynyl)pyridin-2-amine (62 g, 239 mmol) in NMP (100 mL) at a rate to maintain the internal temperature below 100° C. After complete addition the reaction was deemed complete by LCMS. The reaction mixture was allowed to cool to room temperature and poured carefully into saturated brine (700 mL) cooled in an ice bath to 10° C. The precipitate that formed was aged for 45 min at this temperature and isolated by filtration through buchner funnel. The collected precipitate was stirred in ethyl acetate (1 litre) and water then filtered through celite to remove insoluble polymeric material and organic layer was separated. The aqueous layer was further extracted with ethyl acetate and the combined organic layers dried over magnesium sulfate and concentrated to give a brown solid which was triturated by stirring for an hour in hot heptane and then cooling before filtration, to afford 5-Trifluoromethyl-1H-pyrrolo[2,3-b]pyridine as a crystalline solid (26.38 g, 59% yield).

1. temperatureto maintain the internal temperature below 100° C
2. additionAfter complete addition the reaction
3. temperaturecooled in an ice bath to 10° C
4. customThe precipitate that formed
5. customisolated by filtration through buchner funnel
6. filtrationwater then filtered through celite
7. customto remove insoluble polymeric material and organic layer
8. customwas separated
9. extractionThe aqueous layer was further extracted with ethyl acetate
10. dry with materialthe combined organic layers dried over magnesium sulfate
11. concentrationconcentrated
12. customto give a brown solid which
13. customwas triturated
14. temperaturecooling before filtration