Carbon Dioxide → 5-Formyl-2-methylthiophene-3-carboxylic acid

To a solution of 2-(4-bromo-5-methyl-2-thienyl)-1,3-dioxolane (5.0 g) in tetrahydrofuran (50 mL) was added dropwise n-butyl lithium (1.6M hexane solution, 12.5 mL) at −78° C. and, after the dropwise addition, the mixture was stirred for 1 hr. Carbon dioxide was blown into the reaction solution for 30 min. The reaction mixture was warmed to room temperature, saturated aqueous sodium hydrogen carbonate solution was added, and the mixture was extracted with ethyl acetate. The aqueous layer was acidified with 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The obtained residue was dissolved in tetrahydrofuran (50 mL), 1N hydrochloric acid (50 mL) was added, and the mixture was stirred at 50° C. for 1 hr. The reaction mixture was concentrated and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography to give 5-formyl-2-methylthiophene-3-carboxylic acid (1.2 g, yield 36%) as yellow crystals from a fraction eluted with ethyl acetate-hexane (1:1, volume ratio). melting point 173° C.

1. additionafter the dropwise addition
2. extractionthe mixture was extracted with ethyl acetate
3. extractionthe mixture was extracted with ethyl acetate
4. washThe ethyl acetate layer was washed with saturated brine
5. dry with materialdried (MgSO4)
6. concentrationconcentrated
7. dissolutionThe obtained residue was dissolved in tetrahydrofuran (50 mL)
8. addition1N hydrochloric acid (50 mL) was added
9. stirringthe mixture was stirred at 50° C. for 1 hr
10. concentrationThe reaction mixture was concentrated
11. extractionextracted with ethyl acetate
12. washThe ethyl acetate layer was washed with saturated brine
13. dry with materialdried (MgSO4)
14. concentrationconcentrated

ORD record

ord-3b6079d6e62949029adc19c0ccc745a7

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08492405B2