Sodium Hydroxide → 4-Bromo-2-thiophenecarboxylic Acid

Temperature

0 °C

To a solution of 4-bromothiophene-2-carbaldehyde (9.1 g, 48 mmol) in acetone (150 mL) at 0° C. was added Jones' reagent (20 mL of a 2.6 M solution [prepared from CrO3 (26.7 g, 270 mmol) dissolved in H2O (40 mL), and H2SO4 (23 mL)], 52 mmol). After stirring for 30 minutes at 0° C., the ice bath was removed and the reaction was allowed to warm to ambient temperature. After 3 hours stirring at ambient temperature, the reaction was quenched by the addition of 2-propanol. After stirring for 64 hours at ambient temperature, the reaction mixture was diluted with Et2O and filtered through a pad of Florisil. The pad was thoroughly washed with EtOAc, and the filtrate was concentrated under reduced pressure to afford a brown paste. This crude material was dissolved in hot aqueous ethanol, treated with decolorizing carbon and filtered while still hot. Upon cooling an oil separated and formed a suspension. This suspension was treated with solid NaOH (4 g, 100 mmol) and boiled briefly to dissolve the solids. The resulting basic aqueous solution was allowed to cool, and was extracted with Et2O (75 mL). The Et2O extract was discarded. The basic aqueous solution was then acidified by the dropwise addition of concentrated HCl. The acidic aqueous phase was extracted with EtOAc (4×60 mL). The combined EtOAc extracts were washed with brine, and dried over Na2SO4 for 16 hours. The mixture was filtered and concentrated under reduced pressure to afford 4-bromothiophene-2-carboxylic acid as a pale brown solid, which was carried on to the next step without further purification.

1. customthe ice bath was removed
2. temperatureto warm to ambient temperature
3. stirringAfter 3 hours stirring at ambient temperature
4. customthe reaction was quenched by the addition of 2-propanol
5. stirringAfter stirring for 64 hours at ambient temperature
6. additionthe reaction mixture was diluted with Et2O
7. filtrationfiltered through a pad of Florisil
8. washThe pad was thoroughly washed with EtOAc
9. concentrationthe filtrate was concentrated under reduced pressure
10. customto afford a brown paste
11. additiontreated with decolorizing carbon
12. filtrationfiltered while still hot
13. temperatureUpon cooling an oil
14. customseparated
15. customformed a suspension
16. dissolutionto dissolve the solids
17. temperatureto cool
18. extractionwas extracted with Et2O (75 mL)
19. extractionThe Et2O extract
20. additionThe basic aqueous solution was then acidified by the dropwise addition of concentrated HCl
21. extractionThe acidic aqueous phase was extracted with EtOAc (4×60 mL)
22. washThe combined EtOAc extracts were washed with brine
23. dry with materialdried over Na2SO4 for 16 hours
24. filtrationThe mixture was filtered
25. concentrationconcentrated under reduced pressure

ORD record

ord-fa9b700a885d4f06871912cb7b16972b

Source dataset

uspto-grants-2007_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07265131B2