Potassium Carbonate → [(4-bromo-2-fluoro-6-formylphenyl)oxy]acetic Acid

A solution of 5-bromo-3-fluoro-2-hydroxybenzaldehyde (4.57 mmol) in acetonitrile (30 mL) was treated with potassium carbonate (12.66 mmol). The reaction mixture was stirred for 30 min and was then treated with methyl bromoacetate (5.48 mmol). The resulting mixture was stirred at room temperature overnight. Analysis by LCMS indicated the formation of the desired intermediate ester, and the reaction mixture was concentrated to dryness in vacuo. The crude material was dissolved in a 3:1 methanol:water mixture (20 mL) and was heated to 50° C. with stirring for 2 h. The reaction was then cooled to room temperature and was acidified to pH˜3 using 1N aq HCl. The methanol was removed in vacuo and the resulting aqueous suspension was diluted with water (100 mL) and was extracted with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium bicarbonate, dried over magnesium sulfate, filtered, and concentrated in vacuo to give the crude title product. The beige solid was used without further purification (1.05 g, 83% yield). MS(ES)+ m/e 276.9, 278.9 [M+H]+.

1. stirringThe resulting mixture was stirred at room temperature overnight
2. concentrationthe reaction mixture was concentrated to dryness in vacuo
3. dissolutionThe crude material was dissolved in a 3:1 methanol
4. stirringwith stirring for 2 h
5. temperatureThe reaction was then cooled to room temperature
6. customThe methanol was removed in vacuo
7. additionthe resulting aqueous suspension was diluted with water (100 mL)
8. extractionwas extracted with ethyl acetate
9. washThe combined organic layers were washed with saturated aqueous sodium bicarbonate
10. dry with materialdried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo

ORD record

ord-a78665caf5d140b1a6f399a76e12a275

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802864B2