Piperidine → Ethyl 3-nitro-4-(piperidin-1-yl)benzoate

HRID 219781

Reaction equation

F[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][C:3]=1[N+:13]([O-:15])=[O:14].[NH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1>CN(C=O)C.O>[N+:13]([C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:2]=1[N:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])([O-:15])=[O:14]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of ethyl 4-fluoro-3-nitrobenzoate (Clontech 01072, 500 mg; 2.35 mmol; 1 eq.) and piperidine (599.2 mg; 7.04 mmol; 3 eq.) in DMF (2 mL) was heated to 50° C. for 3 hours. The reaction was then allowed to return to RT and diluted with water. It was extracted with EtOAc and the organic phase was dried over sodium sulfate and concentrated in vacuo, affording ethyl 3-nitro-4-piperidin-1-ylbenzoate as a yellow oil. The residue was taken up in THF (15 mL) and lithium hydroxide (280.86 mg; 11.73 mmol; 5 eq.) was added, followed by water (15 mL). The reaction mixture was then stirred at RT for 5 hours. It was concentrated and the residue was diluted with water. The aqueous phase was washed with Et2O and acidified to pH 5 with acetic acid. It was extracted with Et2O and the organic phase was dried over magnesium sulfate and concentrated, affording the title compound as a yellow solid (562 mg, 96%). 1H NMR: (DMSO-d6, 300 MHz) δ 13.07 (s, 1H), 8.29-8.28 (d, J=2.11 Hz, 1H), 8.03-8 (dd, J=8.91 Hz, J=2.20 Hz, 1H), 7.35-7.33 (d, J=8.91 Hz, 1H), 3.15-3.13 (m, 4H), 1.64-1.60 (m, 6H). LC/MS (Method A): 252.9 (M+H)+; 250.9 (M−H)−. HPLC (Method A) Rt 3.69 min (Purity: 99.7%).

Workup

customto return to RT
extractionIt was extracted with EtOAc
dry with materialthe organic phase was dried over sodium sulfate
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-b9d6e5aeb87b4261a8c9995a8d711f38
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08202865B2

Linked notes

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