Reaktion #793711

Reaktionsgleichung

cesium carbonate

2-chloro-4-fluoropyridine

tert-butyl carbamate

cesium carbonate

→

tert-butyl 4-fluoropyridin-2-ylcarbamate

Ausbeute 70.1%

Lösungsmittel

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture was heated
2. 2
   Temperaturat reflux under nitrogen for 7 hours
3. 3
   Temperaturthe reaction was heated a further 7 hours
4. 4
   Filtrationfiltered through Celite
5. 5
   Waschenwashed with ethyl acetate
6. 6
   SonstigeThe filtrate was partitioned between saturated sodium bicarbonate and ethyl acetate
7. 7
   ExtraktionThe aqueous phase was extracted twice with ethyl acetate
8. 8
   WaschenThe combined organic phases were washed with brine
9. 9
   Trocknendried with sodium sulfate
10. 10
    Einengenconcentrated under vacuum
11. 11
    Sonstigepurified by column chromatography

Vorschrift

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).

Quelle