Reaktion #166601

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
   TemperaturThis mixture was heated
2. 2
   Temperaturat reflux under nitrogen for 7 hours
3. 3
   Sonstigethe reaction to completion (
4. 4
   Temperaturheated a further 7 hours)
5. 5
   Filtrationfiltered through Celite
6. 6
   Waschenwashed with ethyl acetate
7. 7
   SonstigeThe filtrate was partitioned between saturated sodium bicarbonate and ethyl acetate
8. 8
   ExtraktionThe aqueous phase was extracted with ethyl acetate twice
9. 9
   WaschenThe combined organic phases were washed with brine
10. 10
    Trocknendried with sodium sulfate
11. 11
    Einengenconcentrated under vacuum
12. 12
    Sonstigepurified by column chromatography

Vorschrift

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).

Quelle