Lithium Hydroxide → 4-(Morpholin-4-yl)-3-nitrobenzoic acid

HRID 1950800Notes

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][O:19][CH2:18][CH2:17]1.[OH-].[Li+]>CN(C=O)C.O.C1COCC1>[N:16]1([C:2]2[CH:12]=[CH:11][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=2[N+:13]([O-:15])=[O:14])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of ethyl 4-fluoro-3-nitrobenzoate (Chontech 01072; 500 mg; 2.35 mmol; 1 eq.) and morpholine (Fluka 69880; 613.06 mg; 7.04 mmol; 3 eq.) in DMF (2 mL) was stirred at 50° C. for 3 hours. The reaction was then allowed to return to room temperature and diluted with water. Extraction with ethyl acetate, drying over sodium sulfate and concentration in vacuo gave a yellow oil. The latter 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 stirred at room temperature for 5 hours. The 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 (548 mg, 93%) as a yellow solid.

Workup

customto return 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 stirred at room temperature for 5 hours
customThe THF 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-dc7dff9f9694402d8aee8c172bc1ba7c
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08404676B2

Reaction notes

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