Cesium carbonate → tert-butyl N-(4-fluoropyridin-2-yl)carbamate

A 2 L flask was charged 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 (2-(dicyclohexylphosphino)-2′,4′,6′-triisopropyl-1,1′-biphenyl) (1.48 g, 3.10 mmol), cesium carbonate (99 g, 588 mmol), and tetrahydrofuran (500 mL) under an atmosphere of dry nitrogen. This mixture was heated at reflux under nitrogen for 7 hours. An additional 1 equivalent of cesium carbonate was added to drive the reaction to completion (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 with ethyl acetate twice. 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. temperatureThis mixture was heated
2. temperatureat reflux under nitrogen for 7 hours
3. customthe reaction to completion (
4. temperatureheated a further 7 hours)
5. filtrationfiltered through Celite
6. washwashed with ethyl acetate
7. customThe filtrate was partitioned between saturated sodium bicarbonate and ethyl acetate
8. extractionThe aqueous phase was extracted with ethyl acetate twice
9. washThe combined organic phases were washed with brine
10. dry with materialdried with sodium sulfate
11. concentrationconcentrated under vacuum
12. custompurified by column chromatography

ORD-Eintrag

ord-1968fdd3c2b6421f94b4cfb6dae4529a

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08841455B2