Reaktion #747292

Reaktionsgleichung

3(S)-(3-chloro-4-fluorophenylamino)pyrrolidine-1-carboxylic acid tert-butyl ester

3-bromopyridine

9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene

sodium tert-butoxide

→

3(S)-[(3-chloro-4-fluorophenyl)pyridin-3-ylamino]pyrrolidine-1-carboxylic acid tert-butyl ester

Lösungsmittel

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture was heated
2. 2
   Temperaturunder reflux under a nitrogen atmosphere for 9 hours
3. 3
   Filtrationthe reaction solution was filtered
4. 4
   workup.ADDITIONWater was added to the filtrate, and extraction with ethyl acetate
5. 5
   TrocknenAfter drying over sodium sulfate and concentration under reduced pressure
6. 6
   Sonstigethe residue was then purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1)
7. 7
   EinengenThe purified product was concentrated under reduced pressure

Vorschrift

To a 10 ml of toluene solution containing 1.0 g of 3(S)-(3-chloro-4-fluorophenylamino)pyrrolidine-1-carboxylic acid tert-butyl ester (3.2 mmol) and 0.75 g of 3-bromopyridine (4.75 mmol) were added 50 mg of 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (XANTPHOS, 0.09 mmol), 21.4 mg of palladium acetate (0.10 mmol) and 11.6 g of sodium tert-butoxide (120 mmol). The mixture was heated under reflux under a nitrogen atmosphere for 9 hours. After cooling to room temperature, the reaction solution was filtered using Celite. Water was added to the filtrate, and extraction with ethyl acetate was conducted. After drying over sodium sulfate and concentration under reduced pressure, the residue was then purified by silica gel column chromatography (n-hexane:ethyl acetate=1:1). The purified product was concentrated under reduced pressure to thereby obtain 1.14 g of oily light yellow 3(S)-[(3-chloro-4-fluorophenyl)pyridin-3-ylamino]pyrrolidine-1-carboxylic acid tert-butyl ester.

Quelle