Reaction #2565

Reaction equation

1-(2-chloroethyl)-4-(4-fluorobenzoyl)piperidine

N-(2-methoxyphenyl)-p-toluenesulfonamide

sodium iodide

sodium hydride

→

title compound

Yield 91.5%

N-{2-[4-(4-Fluorobenzoyl)piperidino]ethyl}-N-(2-methoxyphenyl)-p-toluenesulfonamide

Yield 91.5%

Solvents

DMF

DMF

DMF

Conditions

Workup

1. 1
   Otherat room temperature
2. 2
   workup.WAITat 60° C. for 10 minutes
3. 3
   workup.ADDITIONwas added to the reaction solution at 1 hour intervals at 60° C
4. 4
   Otherwas removed by evaporation
5. 5
   workup.ADDITIONThe thus obtained residue was diluted with water (10 ml)
6. 6
   Extractionextracted with ether
7. 7
   WashThe resulting organic layer was washed with water and saturated brine
8. 8
   Dryingdried on anhydrous sodium carbonate
9. 9
   OtherThereafter, the solvent was removed by evaporation
10. 10
    Otherthe resulting residue was purified by a silica gel column chromatography (ether:hexane=2:1)

Procedure

In an atmosphere of argon, N-(2-methoxyphenyl)-p-toluenesulfonamide (277 mg, 1.0 mmol) and a catalytically effective amount of sodium iodide were dissolved in DMF (3 ml) to which was subsequently added sodium hydride (44 mg, 60%, 1.1 mmol) at room temperature. After stirring at the same temperature for 30 minutes and then at 60° C. for 10 minutes, 1-(2-chloroethyl)-4-(4-fluorobenzoyl)piperidine (324 mg, 1.2 mmol) which has been divided into 3 portions, each being dissolved in DMF (1 ml), was added to the reaction solution at 1 hour intervals at 60° C. After 1.5 hours of additional stirring at the same temperature, DMF was removed by evaporation. The thus obtained residue was diluted with water (10 ml) and extracted with ether. The resulting organic layer was washed with water and saturated brine, and dried on anhydrous sodium carbonate. Thereafter, the solvent was removed by evaporation, and the resulting residue was purified by a silica gel column chromatography (ether:hexane=2:1) to obtain 467 mg (91.5%) of the title compound in the form of colorless oil.

Source