Reaction #2329081

Reaction equation

methanol

sodium hydride

1-(2-Fluoro-4-nitrophenyl)piperidine

→

title compound

Yield 84.0%

1-(2-methoxy-4-nitrophenyl)piperidine

Yield 84.0%

Solvents

N,N-dimethylformamide

N,N-dimethylformamide

Conditions

Workup

1. 1
   Temperaturethe mixture was refluxed for 20 hours
2. 2
   Extractionthe mixture was extracted with ethyl acetate
3. 3
   WashThe ethyl acetate layer was washed with saturated brine
4. 4
   Dryingdried over anhydrous sodium sulfate
5. 5
   OtherThe residue obtained by evaporation of the solvent under reduced pressure
6. 6
   Otherwas purified by column chromatography on silica gel (n-hexane:ethyl acetate=5:1)

Procedure

A solution of methanol (0.178 ml, 10.0 mmol) in N,N-dimethylformamide (1 ml) was added dropwise to a suspension of 60% sodium hydride (0.176 g, 4.40 mmol) in N,N-dimethylformamide (5 ml) under ice cooling, and the mixture was stirred at room temperature for 1 hour. 1-(2-Fluoro-4-nitrophenyl)piperidine (compound of Reference Example 3; 0.448 g, 2.00 mmol) was added to the reaction mixture under ice cooling, and the mixture was refluxed for 20 hours. Ice water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine and dried over anhydrous sodium sulfate. The residue obtained by evaporation of the solvent under reduced pressure was purified by column chromatography on silica gel (n-hexane:ethyl acetate=5:1) to give the title compound (0.395 g, 84%) as a yellow solid.

Source