Reaction #57777

Reaction equation

HCl

NaOH

4-Cyanopyridine

AlCl3

4-chloroaniline

BCl3

→

(2-amino-5-chloro-phenyl)-pyridin-4-yl-methanone

Yield 75.0%

Solvents

DCM

water

Conditions

Workup

1. 1
   Temperaturecooling, over a period of 15 min
2. 2
   workup.STIRRINGstirred for 30 min
3. 3
   TemperatureThe resulting solution was refluxed at 160° C. for 4 h
4. 4
   workup.STIRRINGstirred at room temperature overnight
5. 5
   Temperaturethe mixture was refluxed at 110° C. for 1.5 h
6. 6
   Temperatureto cool down to room temperature
7. 7
   OtherThe resulting two layers were separated
8. 8
   Extractionthe aqueous layer was extracted with DCM three times
9. 9
   Dryingdried over sodium sulfate
10. 10
    OtherAfter removal of the solvent
11. 11
    Washthe resulting solid was washed with ether

Procedure

A solution of 4-chloroaniline (2.0 g, 16 mmol) in 30 mL of TCE was added drop wise to a solution of BCl3 (1M in DCM) (24 ml, 24 mmol) with ice bath cooling, over a period of 15 min and the reaction mixture stirred at that temperature for an additional 10 min. 4-Cyanopyridine (2.0 g, 19 mmol) and AlCl3 (3.0 g, 22 mmol) were added with ice-water cooling. The solution was allowed to warm to room temperature and stirred for 30 min. The resulting solution was refluxed at 160° C. for 4 h and stirred at room temperature overnight. The reaction mixture was then treated with 30 mL of 3N HCl and the mixture was refluxed at 110° C. for 1.5 h. The reaction mixture was allowed to cool down to room temperature and the solution was adjusted to pH12 with 6N NaOH and then diluted water and DCM. The resulting two layers were separated and the aqueous layer was extracted with DCM three times and the organic layers combined and dried over sodium sulfate. After removal of the solvent, the resulting solid was washed with ether to yield (2-amino-5-chloro-phenyl)-pyridin-4-yl-methanone (2.8 g, 75%).

Source