Reaktion #495197

Reaktionsgleichung

(S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one

5-bromo-2-(trifluoromethyl)pyrimidine

(S)-(−)-2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl

Cs2CO3

→

(S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(1-(2-(trifluoromethyl)pyrimidin-5-yl)piperidin-4-yl)pyrrolidin-2-one

Ausbeute 23.2%

Lösungsmittel

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe solution was cooled
2. 2
   Sonstigequenched with water
3. 3
   Extraktionextracted with EtOAc
4. 4
   Trocknendried over MgSO4
5. 5
   Einengenconcentrated
6. 6
   SonstigeDCM gave a white solid
7. 7
   Filtrationthat was filtered
8. 8
   Sonstigedried

Vorschrift

A mixture of (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one (Preparation E; 0.20 g, 0.56 mmol), 5-bromo-2-(trifluoromethyl)pyrimidine (0.15 g, 0.68 mmol), (S)-(−)-2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl (0.076 g, 0.11 mmol), Pd(OAc)2 (0.025 g, 0.11 mmol), and Cs2CO3 (0.92 g, 2.8 mmol) were combined in degassed toluene (6 mL) and stirred in a sealed tube at 110° C. overnight. The solution was cooled, quenched with water, extracted with EtOAc, dried over MgSO4, and concentrated. Flash chromatography of the crude product on silica followed by trituration of the isolated material with 9:1 hexanes:DCM gave a white solid that was filtered and dried. The material was characterized as (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(1-(2-(trifluoromethyl)pyrimidin-5-yl)piperidin-4-yl)pyrrolidin-2-one (0.064 g, 0.13 mmol, 23% yield). Mass spectrum (apci) m/z=502.1 (M+H). Optical purity was not determined.

Quelle