Reaktion #57790

Reaktionsgleichung

HCl

BCl3

1,2-difluoro-4-aminobenzene

NaOH

3-Cyanopyridine

→

(6-Amino-3,4-difluoro-phenyl)-pyridin-3-yl-methanone

Lösungsmittel

water

dichloromethane

trichloroethylene

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstirred for 30 min
2. 2
   TemperaturThe solution was then heated at 80-90° C. for 1 h
3. 3
   TemperaturThe resulting solution was refluxed at 160° C. for 4 hr
4. 4
   workup.STIRRINGstirred at room temprature over night
5. 5
   Temperaturagain refluxed at 110° C. for 1.5 h
6. 6
   TemperaturThe reaction mixture was cooled to RT
7. 7
   SonstigeThe resulting two layers were separated
8. 8
   Extraktionthe aqueous layer was extracted with dichloromethane
9. 9
   Trocknendried over sodium sulfate
10. 10
    Einengenconcentrated
11. 11
    SonstigeThe compound was purified by column chromatography on silica gel
12. 12
    SonstigeHPLC [c18 BDS 25 min column, flow=0.8 ml/min (70:30; ACN:0.1% TFA), rt=4.34 min]

Vorschrift

BCl3 (6.2 ml, 1M in DCM) was added dropwise to 1,2-difluoro-4-aminobenzene (0.5 g, 0.004 mol) in trichloroethylene (6.5 ml) at 0° C., the reaction mixture stirred for 15 min, then 3-Cyanopyridine (0.48 g, 0.005 mol) added and the solution warmed to room temperature and stirred for 30 min. The solution was then heated at 80-90° C. for 1 h. The resulting solution was refluxed at 160° C. for 4 hr, then stirred at room temprature over night, then 3N HCl was added to the reaction mixture and again refluxed at 110° C. for 1.5 h. The reaction mixture was cooled to RT and made basic (pH=12) with 6N NaOH. The reaction mixture was diluted with water and dichloromethane. The resulting two layers were separated and the aqueous layer was extracted with dichloromethane, dried over sodium sulfate and concentrated. The compound was purified by column chromatography on silica gel. 1H NMR (CDCl3): 6.29 (bs, 2H, NH2), 6.56 (m,1H), 7.25 (m,1H), 7.46 (m,1H), 7.93 (m,1H), 8.80 (m,1H), 8.85 (s, 1H). 13C NMR (CDCl3): 104.5, 104.7, 112.7, 121.3, 123.3, 135.1, 136.1, 142.5, 149.3, 149.5, 152.0, 153.8, 153.9, 156.3, 194.7. LC-MS m/e=235 (M+H)+. HPLC [c18 BDS 25 min column, flow=0.8 ml/min (70:30; ACN:0.1% TFA), rt=4.34 min].

Quelle