Réaction #166601

Équation de réaction

cesium carbonate

2-chloro-4-fluoropyridine

tert-butyl carbamate

cesium carbonate

→

tert-butyl 4-fluoropyridin-2-ylcarbamate

Rendement 70.1%

Solvants

tetrahydrofuran

Conditions de réaction

Traitement

1. 1
   TempératureThis mixture was heated
2. 2
   Températureat reflux under nitrogen for 7 hours
3. 3
   Autrethe reaction to completion (
4. 4
   Températureheated a further 7 hours)
5. 5
   Filtrationfiltered through Celite
6. 6
   Lavagewashed with ethyl acetate
7. 7
   AutreThe filtrate was partitioned between saturated sodium bicarbonate and ethyl acetate
8. 8
   ExtractionThe aqueous phase was extracted with ethyl acetate twice
9. 9
   LavageThe combined organic phases were washed with brine
10. 10
    Séchagedried with sodium sulfate
11. 11
    Concentrationconcentrated under vacuum
12. 12
    Autrepurified by column chromatography

Mode opératoire

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).

Source