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

HRID 1691932

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

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

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

Sources & evidence

ORD record: ord-2e91b16b27d145648a4b459fad382340
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08153644B2

Linked notes

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