p-Fluoronitrobenzene → Methyl 1-(4-nitrophenyl)piperidine-4-carboxylate

HRID 1641854Notes

Reaction equation

HRID 1641854 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[CH3:11][O:12][C:13]([CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1)=[O:14].C(N(C(C)C)CC)(C)C>C1COCC1>[CH3:11][O:12][C:13]([CH:15]1[CH2:20][CH2:19][N:18]([C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[CH2:17][CH2:16]1)=[O:14]

Participants

5

Reactant 3

HCID 9590p-FluoronitrobenzeneHCID 81531DiisopropylethylamineHCID 424914Methyl isonipecotate

Product 1

HCID 345002Methyl 1-(4-nitrophenyl)piperidine-4-carboxylateYield 37.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 4-fluoronitrobenzene (0.70 g, 4.96 mmol) in THF (8 mL) was added piperadine-4-carboxylic acid methyl ester (0.71 g, 4.96 mmol) and diisopropylethylamine (0.66 g, 5.11 mmol). The mixture was heated in a microwave oven at 150° C. for 1.5 hr. The resulting mixture was extracted with ethyl acetate and hydrochloric acid (0.2 N). The organic layer was washed with brine and concentrated sodium bicarbonate solution. After the evaporation of solvents, the residue was purified through a Biotage flash column chromatography using ethyl acetate and hexanes (1:1 ratio) to give a yellow solid as 1-(4-nitrophenyl)-piperidine-4-carboxylic acid methyl ester (490 mg). 1H-NMR is consistent with the structure.

Workup

  1. extractionThe resulting mixture was extracted with ethyl acetate and hydrochloric acid (0.2 N)
  2. washThe organic layer was washed with brine and concentrated sodium bicarbonate solution
  3. customAfter the evaporation of solvents
  4. customthe residue was purified through a Biotage flash column chromatography

Sources & evidence

ORD record
ord-e70ec3731a904dd5af0c318acc04c0d5
Source dataset
uspto-grants-2012_02
Patent number
US08115011B2

Reaction notes

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