Reaction #57785

Reaction equation

HCl

BCl3

1,2-difluoro-4aminobenzene

NaOH

4-Cyanopyridine

→

title compound

(2-Amino-4,5-difluoro-phenyl)-pyridin4-yl-methanone

Solvents

water

DCM

trichloroethylene

Conditions

Workup

1. 1
   workup.STIRRINGstirred for 30 min
2. 2
   TemperatureThe solution was then heated at 80-90° C. for 1 h
3. 3
   TemperatureThe resulting solution was refluxed at 160° C. for 4 hr
4. 4
   workup.STIRRINGstirred at RT over night
5. 5
   Temperaturerefluxed at 110° C. for 1.5 h
6. 6
   TemperatureThe reaction mixture was cooled to RT
7. 7
   OtherThe resulting two layers were separated
8. 8
   Extractionthe aqueous layer was extracted with DCM
9. 9
   Dryingdried over sodium sulphate
10. 10
    Concentrationconcentrated
11. 11
    OtherThe compound was purified by column chromatography

Procedure

BCl3 (6.2 ml, 1M in DCM) was added drop wise to 1,2-difluoro-4aminobenzene (0.5 g, 0.004 mol) in trichloroethylene (6.5 ml) at 0° C. and this mixture stirred for 15 min. 4-Cyanopyridine (0.48 g, 0.005 mol) was added and the solution was warmed to RT 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 and stirred at RT over night. 3N HCl was added to the reaction mixture and 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 DCM. The resulting two layers were separated and the aqueous layer was extracted with DCM, dried over sodium sulphate and concentrated. The compound was purified by column chromatography using silica gel to yield title compound.

Source