反应详情

A flask was charged with 2-chloro-4-fluoropyridine (20 g, 152 mmol), tert-butyl carbamate (89 g, 760 mmol), tris(dibenzylideneacetone)dipalladium (1.39 g, 1.52 mmol), X-PHOS (1.48 g, 3.10 mmol), cesium carbonate (99 g, 588 mmol), and tetrahydrofuran (500 mL) under an atmosphere of dry nitrogen. The mixture was heated at reflux under nitrogen for 7 hours. A further 1 equivalent of cesium carbonate was added and the reaction was heated a further 7 hours. The mixture was cooled to ambient temperature, filtered through Celite and washed with ethyl acetate. The filtrate was partitioned between saturated sodium bicarbonate and ethyl acetate. The aqueous phase was extracted twice with ethyl acetate. The combined organic phases were washed with brine and dried with sodium sulfate, concentrated under vacuum, and purified by column chromatography to give tert-butyl 4-fluoropyridin-2-ylcarbamate as a pale yellow solid (22.6 g).

1. temperatureThe mixture was heated
2. temperatureat reflux under nitrogen for 7 hours
3. temperaturethe reaction was heated a further 7 hours
4. filtrationfiltered through Celite
5. washwashed with ethyl acetate
6. customThe filtrate was partitioned between saturated sodium bicarbonate and ethyl acetate
7. extractionThe aqueous phase was extracted twice with ethyl acetate
8. washThe combined organic phases were washed with brine
9. dry with materialdried with sodium sulfate
10. concentrationconcentrated under vacuum
11. custompurified by column chromatography