p-Fluoronitrobenzene → Piperidine, 1-methyl-4-(4-nitrophenoxy)-4-(phenylmethyl)-

HRID 1156027Notes

Reaction equation

HRID 1156027 reaction equation
[CH2:1]([C:8]1([OH:15])[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[H][H].F[C:21]1[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=1>CN(C)C=O>[CH2:1]([C:8]1([O:15][C:21]2[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=2)[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 9590p-FluoronitrobenzeneHCID 24758Sodium hydrideHCID 10536240HCID 10536240, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 3060391Piperidine, 1-methyl-4-(4-nitrophenoxy)-4-(phenylmethyl)-Yield 61.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 40.0 g of 4-benzyl-1-methylpiperidin-4-ol in 120 ml of absolute dimethylformamide is added dropwise to a suspension of 8.76 g of sodium hydride (80% strength in oil) in 200 ml of absolute dimethylformamide, while stirring and with exclusion of moisture. During this addition, evolution of hydrogen occurs. When the addition has ended, the mixture is stirred at room temperature for 2 hours, 31.6 g of 4-fluoronitrobenzene are added dropwise thereto, and the mixture is stirred at 50° C. for a further 2 hours. The resulting brown reaction mixture is then poured into 350 ml of ice-water and is stirred for 30 minutes; a precipitate (which has separated out) is filtered off and washed with water and petroleum ether. This crude product is dissolved in 150 ml of boiling ethanol, decanted to remove undissolved material, treated with active charcoal and filtered. 100 ml of petroleum ether are added slowly to the cooled filtrate, and the formed precipitate is filtered off and washed with petroleum ether. 38.9 g of the cream-colored title compound of m.p. 116° to 117° C. are obtained by successive concentration of the filtrate.

Workup

  1. additionWhen the addition
  2. stirringthe mixture is stirred at room temperature for 2 hours
  3. stirringthe mixture is stirred at 50° C. for a further 2 hours
  4. stirringis stirred for 30 minutes
  5. customa precipitate (which has separated out)
  6. filtrationis filtered off
  7. washwashed with water and petroleum ether
  8. dissolutionThis crude product is dissolved in 150 ml of boiling ethanol
  9. customdecanted
  10. customto remove undissolved material
  11. additiontreated with active charcoal
  12. filtrationfiltered
  13. addition100 ml of petroleum ether are added slowly to the cooled filtrate
  14. filtrationthe formed precipitate is filtered off
  15. washwashed with petroleum ether

Sources & evidence

ORD record
ord-768512d78c6446489bf82dc85fc9cd99
Source dataset
uspto-grants-1982_06
Patent number
US04333942

Reaction notes

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