Carbon Dioxide → 4-Methylthiophene-3-carboxylic acid

Temperature

-78 °C

To a stirred solution of 3-bromo-4-methylthiophene (2.7 g, 15.6 mmol) in THF (35 mL) was added n-BuLi (1.6 M in hexane, 14.6 mL, 23.3 mmol) at −78° C. dropwise over a period of 15 min and the mixture was stirred at −78° C. for 30 min. The CO2 (gaseous) was passed through the reaction mixture for 10 min and the mixture was stirred at the same temperature for 20 min. Thereafter, the reaction mixture was warmed to 0° C., quenched with aqueous 1 M NaOH (60 mL) and washed with EtOAc (2×50 mL). The aqueous layer was acidified to pH ˜5 and extracted with DCM (2×50 mL). The combined organic layers were washed with water (100 mL), brine (100 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 8% MeOH/DCM as eluent) to provide compound A56-1 (1.5 g, 70%) as a white solid.

1. stirringthe mixture was stirred at the same temperature for 20 min
2. temperatureThereafter, the reaction mixture was warmed to 0° C.
3. customquenched with aqueous 1 M NaOH (60 mL)
4. washwashed with EtOAc (2×50 mL)
5. extractionextracted with DCM (2×50 mL)
6. washThe combined organic layers were washed with water (100 mL), brine (100 mL)
7. dry with materialdried over anhydrous Na2SO4
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by column chromatography (silica gel, 8% MeOH/DCM as eluent)
10. customto provide compound A56-1 (1.5 g, 70%) as a white solid

ORD record

ord-bbffdb27d6504c7ead4ae168e3d3f1b1

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365522B2