Reaktion #82225

Reaktionsgleichung

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

4-chloro-3-fluoropyridine

p-toluenesulfonic acid hydrate

4-chloro-3-fluoropyridine hydrochloride

sodium bicarbonate

phenol

→

desired product

1,3-Dihydro-1-[(3-fluoro-4-pyridinyl)propylamino]-2H-indol-2-one

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturHeating
2. 2
   workup.ADDITIONwas added
3. 3
   Temperaturheating
4. 4
   TemperaturUpon cooling to room temperature
5. 5
   SonstigeThe layers were separated
6. 6
   Extraktionthe organic layer extracted with dilute aqueous sodium bicarbonate (2×)
7. 7
   ExtraktionThe combined aqueous layers were back-extracted with dichloromethane and ether
8. 8
   WaschenThe combined organic layers were washed with brine
9. 9
   Trocknendried (K2CO3)
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated
12. 12
    SonstigePurification via flash column chromatography (silica gel, 2% triethylamine/ether)

Vorschrift

To a stirred solution consisting of 1,3-dihydro-1-propylamino-2H-indol-2-one (5.06 g), phenol (13.2 g) and p-toluenesulfonic acid hydrate (0.25 g), heated at 150° C., was added 4-chloro-3-fluoropyridine hydrochloride (5.37 g). Heating was continued at 150° C. for 10.75 hours at which time additional 4-chloro-3-fluoropyridine (2.05 g) was added and heating continued an additional 6.5 hours. Upon cooling to room temperature, the reaction mixture was dissolved in dichloromethane and dilute aqueous sodium bicarbonate. The layers were separated and the organic layer extracted with dilute aqueous sodium bicarbonate (2×). The combined aqueous layers were back-extracted with dichloromethane and ether. The combined organic layers were washed with brine, dried (K2CO3), filtered, and concentrated. Purification via flash column chromatography (silica gel, 2% triethylamine/ether) and another column (silica gel, EtOAc) afforded the desired product as a solid.

Quelle