Nitric Acid → 1-Methyl-4-(4-nitrophenyl)piperidine

HRID 2109630Notes

Reaction equation

HRID 2109630 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.OS(O)(=O)=O.[N+:19]([O-])([OH:21])=[O:20].[OH-].[Na+]>>[CH3:1][N:2]1[CH2:3][CH2:4][CH:5]([C:8]2[CH:13]=[CH:12][C:11]([N+:19]([O-:21])=[O:20])=[CH:10][CH:9]=2)[CH2:6][CH2:7]1

Participants

5

Reactant 4

HCID 944Nitric AcidHCID 1118Sulfuric Acid2×HCID 14798Sodium HydroxideHCID 202391Piperidine, 1-methyl-4-phenyl-

Product 1

HCID 219595311-Methyl-4-(4-nitrophenyl)piperidine

Conditions

Temperature
0 °C

Procedure

To 1-methyl-4-phenylpiperidine (2.663 g, 15.19 mmol, Step B) was added carefully H2SO4 (15.2 ml). The reaction was cooled in an ice bath and a solution of H2SO4 (1.66 ml) and fuming HNO3 (0.67 ml, 15.95 mmol) was added dropwise over 45 min. The mix was stirred at 0° C. for 3 h then at RT for 1.5 h before being poured over about 90 g ice and basified with 24 g solid NaOH. The mix was extracted with CH2Cl2. The organic layer was washed with H2O, dried over Na2SO4, and concentrated in vacuo. The crude was eluted on a silica gel column with a MeOH/CH2Cl2 gradient to yield 1-methyl-4-(4-nitrophenyl)piperidine which was hydrogenated under H2 to furnish the title compound.

Workup

  1. temperatureThe reaction was cooled in an ice bath
  2. extractionThe mix was extracted with CH2Cl2
  3. washThe organic layer was washed with H2O
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. washThe crude was eluted on a silica gel column with a MeOH/CH2Cl2 gradient

Sources & evidence

ORD record
ord-8ce1092581a04abb82ee34d536570f42
Source dataset
uspto-grants-2009_04
Patent number
US07514564B2

Reaction notes

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