Potassium Carbonate → [3-(4-Bromo-2-formyl-phenoxy)-phenyl]-acetic acid methyl ester

HRID 1969017Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:12])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([OH:11])[CH:6]=1.[Br:13][C:14]1[CH:15]=[CH:16][C:17](F)=[C:18]([CH:21]=1)[CH:19]=[O:20].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1>[CH3:1][O:2][C:3](=[O:12])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:17]2[CH:16]=[CH:15][C:14]([Br:13])=[CH:21][C:18]=2[CH:19]=[O:20])[CH:6]=1

Participants

Conditions

Temperature: 100 °C

Procedure

(3-Hydroxy-phenyl)-acetic acid methyl ester (1.44 g, 8.66 mmol), 5-bromo-2-fluorobenzaldehyde (1.76 g, 8.66 mmol), and potassium carbonate (2.39 g, 17.32 mmol) were combined in 1,4-dioxane (18 mL) and heated to 100° C. overnight. Some starting material was still observed by analytical LCMS, so additional potassium carbonate (0.6 g, 4.3 mmol) was added, and the reaction was stirred at 100° C. for 4 hours. The mixture was cooled to room temperature and partitioned between EtOAc and H2O. Brine was added to facilitate separation, and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried and concentrated, and the residue was purified by silica gel chromatography (10-30% EtOAc in hexanes) to give the title compound.

Workup

additionwas added
temperatureThe mixture was cooled to room temperature
custompartitioned between EtOAc and H2O
additionBrine was added
customseparation
extractionthe aqueous layer was extracted twice with EtOAc
customThe combined organic layers were dried
concentrationconcentrated
customthe residue was purified by silica gel chromatography (10-30% EtOAc in hexanes)

Sources & evidence

ORD record: ord-5b47407bf7c9481e93982fc1d507563a
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08426449B2

Reaction notes

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