Acetic Acid → 4-Bromofuran-2-carboxylic acid

A 500 mL three-necked round-bottom flask fitted with an overhead mechanical stirrer and reflux condenser was charged with 4,5-dibromo-furan-2-carboxylic acid (57.0 g, 211 mmol), H2O (168 mL), and HOAc (42 mL). The third neck of the flask was stoppered and the suspension was heated to reflux with a temperature controlled heating mantle held at 125-130° C. Zn dust (24.9 g, 381 mmol) (previously ground in a mortar and pestle to break up lumps) was added portionwise over 50 minutes. Subsequent portions are added after most of the previously added portion has disappeared. After the first portions of the Zn were added, all of the 4,5-dibromofuran-2-carboxylic acid dissolves to give a pale brown solution. Twenty-five minutes after the conclusion of the zinc addition a thick grey-white slurry had formed. HPLC analysis of the reaction slurry at this time indicated complete consumption of the starting 4,5-dibromofuran-2-carboxylic acid and conversion to the desired product. After 35 minutes, heating was discontinued, and the slurry was allowed to cool to ambient temperature. After cooling to ambient temperature the reaction slurry was diluted with cold H2O (175 mL), cooled in an ice bath, and then filtered. The white and grey solids were rinsed with cold H2O, and dried on the filter for 3 hours. The product/Zn mixture was then pumped down under high vacuum with gentle heating to afford white-grey flakes. A portion of the resulting solids (37.3 g) was dissolved in warm acetone (1.8 L, solubility about 20 g/L). The resulting solution was filtered to remove residual zinc dust, and then concentrated under reduced pressure to afford 4-bromo-furan-2-carboxylic acid as a white powder. This material was carried on to the acid chloride formation without purification. 1H-NMR (400 MHz, DMSO-d6): δ 7.96 (1H, d, J=0.8 Hz), 7.04 (1H, d, J=0.8 Hz).

1. customA 500 mL three-necked round-bottom flask fitted with an overhead mechanical stirrer
2. temperaturereflux condenser
3. temperaturethe suspension was heated
4. temperatureto reflux with a temperature
5. temperaturecontrolled heating mantle
6. customheld at 125-130° C
7. additionwas added portionwise over 50 minutes
8. additionSubsequent portions are added after most of the previously added portion
9. customto give a pale brown solution
10. customhad formed
11. customconsumption of the starting 4,5-dibromofuran-2-carboxylic acid and conversion to the desired product
12. temperatureheating
13. temperatureAfter cooling to ambient temperature the reaction slurry
14. additionwas diluted with cold H2O (175 mL)
15. temperaturecooled in an ice bath
16. filtrationfiltered
17. washThe white and grey solids were rinsed with cold H2O
18. customdried on the
19. filtrationfilter for 3 hours
20. temperaturewith gentle heating
21. customto afford white-grey flakes
22. filtrationThe resulting solution was filtered
23. customto remove residual zinc dust
24. concentrationconcentrated under reduced pressure

ORD record

ord-c3e182bfdabc4383bcc26570f209dd6a

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08703805B2