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

HRID 887584Notes

Reaction equation

HRID 887584 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) 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-4cabdd3cc71749d99957b486cc25543a
Source dataset
uspto-grants-2012_08
Patent number
US08247430B2

Reaction notes

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