Reaktion #215860

Reaktionsgleichung

sodium hydroxide

1,3-dihydro-1-(propylamino)-2H-indol-2-one

phenol

4-bromopyridine hydrochloride

→

1,3-dihydro-1-(propyl-4-pyridinylamino)-2H-indol-2-one

Ausbeute 14.4%

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigepreheated to 150° C. under nitrogen
2. 2
   TemperaturHeating
3. 3
   ExtraktionThe product was extracted four times with ethyl acetate
4. 4
   Extraktionthe combined organic layers back-extracted with dilute aqueous sodium hydroxide
5. 5
   Waschenwashed with brine
6. 6
   Trocknendried (K2CO3)
7. 7
   FiltrationFiltration and concentration
8. 8
   Sonstigegave the crude product
9. 9
   SonstigePurification via flash column chromatography (silica gel, EtOAc), preparative high performance liquid chromatography (HPLC) (silica gel, EtOAc→2% Et3N/0-7% MeOH/EtOAc)
10. 10
    SonstigeRecrystallization from ethyl acetate-pentane

Vorschrift

To a stirred solution of 1,3-dihydro-1-(propylamino)-2H-indol-2-one (10.4 g) and phenol (30.8 g), preheated to 150° C. under nitrogen, was added 4-bromopyridine hydrochloride (11.04 g) over 5 min. Heating was continued for 7 hours at which time the reaction mixture was cooled to room temperature and made basic by slow addition of dilute aqueous sodium hydroxide. The product was extracted four times with ethyl acetate and the combined organic layers back-extracted with dilute aqueous sodium hydroxide, washed with brine, and dried (K2CO3). Filtration and concentration gave the crude product. Purification via flash column chromatography (silica gel, EtOAc), preparative high performance liquid chromatography (HPLC) (silica gel, EtOAc→2% Et3N/0-7% MeOH/EtOAc), and a third column (alumina, EtOAc) followed. Recrystallization from ethyl acetate-pentane afforded 2.10 g (14%) of 1,3-dihydro-1-(propyl-4-pyridinylamino)-2H-indol-2-one, as a solid, m.p. 140°-143° C.

Quelle