Reaktion #747295

Reaktionsgleichung

sodium bis(trimethylsilyl)amide

toluene

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

2-chloro-4-fluorobenzonitrile

→

white amorphous solid

Ausbeute 77.7%

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

Ausbeute 77.7%

Lösungsmittel

diethyl ether

Water

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture was heated
2. 2
   Temperaturunder reflux under a nitrogen atmosphere for 8 hours
3. 3
   TrocknenAfter drying over sodium sulfate and concentration under reduced pressure
4. 4
   Sonstigethe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1)
5. 5
   EinengenThe purified product was concentrated to dryness under reduced pressure

Vorschrift

To an anhydrous toluene solution containing 3(S)-[(3-chloro-4-fluorophenyl)amino]pyrrolidine-1-carboxylic acid tert-butyl ester (0.50 g, 1.6 mmol) and 2-chloro-4-fluorobenzonitrile (0.30 g, 1.9 mmol) was added a 1.45 ml tetrahydrofuran solution containing sodium bis(trimethylsilyl)amide (1.1 M) using a syringe. The mixture was heated under reflux under a nitrogen atmosphere for 8 hours and cooled to room temperature. Water was added to the reaction solution, and extraction with diethyl ether was conducted. After drying over sodium sulfate and concentration under reduced pressure, the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1). The purified product was concentrated to dryness under reduced pressure to thereby obtain 0.56 g of white amorphous solid 3(S)-[(3-chloro-4-cyanophenyl)-(3-chloro-4-fluorophenyl)amino]pyrrolidine-1-carboxylic acid tert-butyl ester.

Quelle