Lithium Hydroxide → 3-Nitro-4-(piperidin-1-yl)benzoic acid

HRID 336225Notes

Reaction equation

F[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8]CC)=[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.[OH-].[Li+]>CN(C=O)C.O.C1COCC1>[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]([OH:8])=[O:7])([O-:15])=[O:14]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of ethyl 4-fluoro-3-nitrobenzoate (Chontech 01072; 500 mg; 2.35 mmol; 1 eq.) and piperidine (Fluka 80640; 599.18 mg; 7.04 mmol; 3 eq.) in DMF (2 mL) was stirred at 50° C. for 3 hours. The reaction was then allowed to cool to room temperature and diluted with water. Extraction with ethyl acetate, drying over sodium sulfate and concentration in vacuo gave a yellow oil. The oil 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 room temperature for 5 hours. THF was evaporated and the residue diluted with water. The aqueous phase was washed with Et2O and acidified to pH 5 with acetic acid. Extraction with Et2O followed by drying over magnesium sulfate and concentration in vacuo afforded the title compound (562 mg, 96%) as a yellow solid.

Workup

temperatureto cool to room temperature
extractionExtraction with ethyl acetate
dry with materialdrying over sodium sulfate and concentration in vacuo
customgave a yellow oil
stirringThe reaction mixture was then stirred at room temperature for 5 hours
customTHF was evaporated
additionthe residue diluted with water
washThe aqueous phase was washed with Et2O
extractionExtraction with Et2O
dry with materialby drying over magnesium sulfate and concentration in vacuo

Sources & evidence

ORD record: ord-565e5ed2a9154c37b74a6f2f31d1d32a
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889668B2

Reaction notes

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