Dimethylformamide → 3-((5-Chloropyridin-2-yl)oxy)benzoic acid

HRID 1422833Notes

Reaction equation

CN(C)C=O.C[O:7][C:8](=[O:16])[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([OH:15])[CH:10]=1.CC(C)([O-])C.[K+].Br[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][N:25]=1>O>[Cl:30][C:27]1[CH:28]=[CH:29][C:24]([O:15][C:11]2[CH:10]=[C:9]([CH:14]=[CH:13][CH:12]=2)[C:8]([OH:7])=[O:16])=[N:25][CH:26]=1

Participants

Conditions

Temperature: 130 °C

Procedure

To a dimethylformamide (100 mL) solution of 3-hydroxy-benzoic acid methyl ester (3.5 g, 23 mmol) was added potassium t-butoxide (3.2 g, 28 mmol). Upon stirring the reaction at room temperature for 15 min, 2-bromo-5-chloro-pyridine was added. The reaction was heated to 130° C. for 15 h. Crude reaction mass was added to water, and extracted with diethyl ether to remove unhydrolyzed methyl ester, 3-(5-chloro-pyridin-2-yloxy)-benzoic acid methyl ester (2.5 g). The aqueous layer was acidified to pH 4.0 and product was extracted with ethyl acetate to give 3-(5-chloro-pyridin-2-yloxy)-benzoic acid (2.0 g). Saponification of methyl ester (2.5 g, 9.4 mmol) using NaOH (1.0 g, 25 mmol) in methanol:THF:water (1:1:1, 60 mL) furnished additional 2.0 g of 3-(5-chloro-pyridin-2-yloxy)-benzoic acid.

Workup

customthe reaction at room temperature for 15 min
customCrude reaction mass
extractionextracted with diethyl ether
customto remove unhydrolyzed methyl ester, 3-(5-chloro-pyridin-2-yloxy)-benzoic acid methyl ester (2.5 g)
extractionwas extracted with ethyl acetate

Sources & evidence

ORD record: ord-6de604da82a04278a13d11799afc8fd7
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927549B2

Reaction notes

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