Carbon Dioxide → thiophene-2,3-dicarboxylic acid

Temperature

-78 °C

A dry, 2 L, 3-necked, round-bottomed flask was equipped with a mechanical stirrer and addition funnel. To the flask was added 2-thiophenecarboxylic acid (25 g, 195 mmol) in anhydrous THF (500 mL) under argon. The mixture was cooled to −78° C. with a dry ice-isopropanol bath and allowed to stir for 30 min. n-Butyllithium in Hexanes (2.5 M, 172 mL) was added dropwise over 30 min. The reaction was kept at −78° C. for an additional hour with stirring then placed under an atmosphere of dry carbon dioxide. With addition of the carbon dioxide the reaction became thick. The reaction remained at −78° C. for an additional hour before warming to −10° C. The reaction was quenched with 2 N HCl (213 mL) and allowed to reach rt. The layers were separated and the aqueous layer was extracted with EtOAc (3×200 mL). The organic layers were combined, dried (Na2SO4) and concentrated by rotary evaporation. The brown solid was crystallized from hot isopropanol and dried overnight under vacuum. Desired thiophene-2,3-dicarboxylic acid was obtained (27.3 g, 159 mmol; 82% yield); 1H NMR (DMSO-d6) 7.69 (d, J=1.5, 1), 7.38 (d, J=4.8, 1); ES MS (M+H)+=173; TLC (Chloroform-MeOH-water, 6:4:1); Rf=0.74.

1. customA dry, 2 L, 3-necked, round-bottomed flask was equipped with a mechanical stirrer and addition funnel
2. additionwas added dropwise over 30 min
3. waitThe reaction was kept at −78° C. for an additional hour
4. waitThe reaction remained at −78° C. for an additional hour
5. temperaturebefore warming to −10° C
6. customThe reaction was quenched with 2 N HCl (213 mL)
7. customto reach rt
8. customThe layers were separated
9. extractionthe aqueous layer was extracted with EtOAc (3×200 mL)
10. dry with materialdried (Na2SO4)
11. concentrationconcentrated by rotary evaporation
12. customThe brown solid was crystallized from hot isopropanol
13. customdried overnight under vacuum

ORD record

ord-2a54bac0c0c9467aa1d92283cd639bda

Source dataset

uspto-grants-2004_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06689883B1