Tetrahydrofuran → Phenyl-(pyridin-3-yloxy)acetic acid methyl ester

Reaction equation

[Na].[OH:2][C:3]1[CH:4]=[N:5][CH:6]=[CH:7][CH:8]=1.Br[CH:10]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:11]([OH:13])=[O:12].O1CCC[CH2:21]1>>[CH3:21][O:13][C:11](=[O:12])[CH:10]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[O:2][C:3]1[CH:4]=[N:5][CH:6]=[CH:7][CH:8]=1

Participants

Reactant 3

HCID 8028Tetrahydrofuran

HCID 97919Bromo(phenyl)acetic acid

HCID 667964713-Hydroxypyridine sodium salt

Product 1

HCID 69849520Phenyl-(pyridin-3-yloxy)acetic acid methyl ester

Procedure

To a slurry of 3-hydroxypyridine sodium salt, 4.6 g (26.4 mmol) in 200 mL of tetrahydrofuran was added 5.0 g (22.0 mmol) of alpha-bromophenylacetic acid. The reaction mixture was refluxed for two hours, cooled to rt. and concentrated to dryness. The residue was partitioned between 20% isopropanol/chloroform and water. The mixture was washed with saturated NaHCO3, washed with brine, dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by column chromatography using MeOH/chloroform as eluent and concentrated to dryness to give 2.8 g of the desired mixture of isomers as a dark oil. MS (ion spray) 244.1 (M+).