Methyl chloroacetate → 7-Bromo-5-fluorobenzofuran-2-carboxylic acid

HRID 535675

Reaction equation

Cl[CH2:2][C:3]([O:5]C)=[O:4].[Br:7][C:8]1[C:9]([OH:17])=[C:10]([CH:13]=[C:14]([F:16])[CH:15]=1)[CH:11]=O.C(=O)([O-])[O-].[K+].[K+].[OH-].[K+]>O1CCCC1.O>[Br:7][C:8]1[C:9]2[O:17][C:2]([C:3]([OH:5])=[O:4])=[CH:11][C:10]=2[CH:13]=[C:14]([F:16])[CH:15]=1

Participants

Conditions

Temperature: 130 °C

Procedure

Methyl chloroacetate (7.6 mL, 86.8 mmol) was added to a mixture of 3-bromo-5-fluoro-2-hydroxy-benzaldehyde (9.5 g, 43.4 mmol), tetra-N-butyl-ammonium iodide (1.6 g, 4.34 mmol) and anhydrous potassium carbonate (24 g, 174 mmol). The reaction mixture was heated at 130° C. for 4 h, cooled to 0° C., diluted with tetrahydrofuran (100 mL) and then potassium hydroxide (17 g, 303 mmol) in water (100 mL). The mixture was stirred at rt for 18 h and then, concentrated under reduced pressure. The residue was acidified with HCl and extracted with ethyl acetate. The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The crude compound was purified by flash chromatography (SiO2; toluene/EtOAc, 40/1) to give 7.0 g (63%) of the product.

Workup

temperaturecooled to 0° C.
concentrationconcentrated under reduced pressure
extractionextracted with ethyl acetate
dry with materialThe combined organic extracts were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe crude compound was purified by flash chromatography (SiO2; toluene/EtOAc, 40/1)

Sources & evidence

ORD record: ord-5e519e47b4254bf38cafbd0db2f6a7ce
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08859534B2

Linked notes

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