Hydrochloric Acid → 1-(4-Nitrophenyl)piperidine-4-carboxylic acid

HRID 2236828Notes

Reaction equation

HRID 2236828 reaction equation
[OH-].C([N+](CCCC)(CCCC)CCCC)CCC.[NH:19]1[CH2:27][CH2:26][CH:22]([C:23]([O-:25])=[O:24])[CH2:21][CH2:20]1.C([N+](CCCC)(CCCC)CCCC)CCC.F[C:46]1[CH:51]=[CH:50][C:49]([N+:52]([O-:54])=[O:53])=[CH:48][CH:47]=1.C(=O)([O-])[O-].[K+].[K+].Cl>CO.CS(C)=O.O>[N+:52]([C:49]1[CH:50]=[CH:51][C:46]([N:19]2[CH2:27][CH2:26][CH:22]([C:23]([OH:25])=[O:24])[CH2:21][CH2:20]2)=[CH:47][CH:48]=1)([O-:54])=[O:53]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 9590p-FluoronitrobenzeneHCID 11430Potassium CarbonateHCID 2723671Tetrabutylammonium HydroxideHCID 86619595HCID 86619595, compound

Product 1

HCID 27672651-(4-Nitrophenyl)piperidine-4-carboxylic acidYield 88%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

To a suspension of isonipocotic acid (8.3 g, 64 mmol) in methanol (250 mL) is added tetrabutylammonium hydroxide (40% aqueous solution, 42 mL). Solvents were then removed under reduced pressure. Residual water is removed by azeotropic distillation with toluene. The semisolid tetrabutylammonium isonipecotate is dried under high vacuum. To a solution of tetrabutylammonium isonipecotate (64 mmol) in dimethylsulfoxide (150 mL) is added 4-fluoronitrobenzene (7.5 mL, 71 mmol) and potassium carbonate (9.6 g, 70 mmol). The reaction mixture is heated in a 75° C. oil bath for three hours and then allowed to cool to room temperature. Water is added, followed by concentrated hydrochloric acid to bring the mixture to pH 6. The precipitated material is collected by filtration, washed with acetonitrile, and dried under house vacuum to provide 1-(4-nitrophenyl)piperidine-4-carboxylic acid as a yellow powder (14 g, 88%).

Workup

  1. customSolvents were then removed under reduced pressure
  2. customResidual water is removed by azeotropic distillation with toluene
  3. dry with materialThe semisolid tetrabutylammonium isonipecotate is dried under high vacuum
  4. temperatureto cool to room temperature
  5. filtrationThe precipitated material is collected by filtration
  6. washwashed with acetonitrile
  7. customdried under house vacuum

Sources & evidence

ORD record
ord-209f83bc7c384c8aa82d85f1c4b16978
Source dataset
uspto-grants-2010_05
Patent number
US07713994B2

Reaction notes

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