Water → 5-Bromo-2,4-dimethylthiophene-3-carboxylic acid

Temperature

10 °C

A solution of bromine (0.73 mL, 2.25 g, 14 mmol) in glacial acetic acid (8 mL) was added to a solution of 2,4-dimethylthiophene-3-carboxylic acid (2.1 g, 13 mmol) in glacial acetic acid (24 mL) at 6° C. Upon completion, the reaction was stirred at 10° C. for an hour, diluted with glacial acetic acid (30 mL), stirred for 14 hours at room temperature, poured into water (400 mL) and extracted with ether (3×40 mL). The combined ethereal extracts were extracted with dilute sodium hydroxide (0.2 N, 3×30 mL). The combined basic extracts were cooled in an ice bath and then acidified to pH 3 using concentrated hydrochloric acid. Precipitated solids were extracted with ether (3×40 mL). Pooled organic extracts were washed with water (50 mL) and brine (50 mL), dried over magnesium sulphate and concentrated under reduced pressure. The residue was recrystallised from ethyl acetate/hexane to give product as an amorphous white solid (2.7 g, 85%): mp 183-184° C.; 1H NMR (CDCl3) δ 2.67 (s, 3H), 2.38 (s, 3H); EI/MS 235 m/e (M+); IR (liq film) 1674 cm−1; Calcd. for C7H7BrO2S: C, 35.8; H, 3.00; S, 13.6; Found: C, 35.8; H, 2.99; N, 13.5.

1. stirringstirred for 14 hours at room temperature
2. extractionextracted with ether (3×40 mL)
3. extractionThe combined ethereal extracts were extracted with dilute sodium hydroxide (0.2 N, 3×30 mL)
4. temperatureThe combined basic extracts were cooled in an ice bath
5. customPrecipitated solids
6. extractionwere extracted with ether (3×40 mL)
7. washPooled organic extracts were washed with water (50 mL) and brine (50 mL)
8. dry with materialdried over magnesium sulphate
9. concentrationconcentrated under reduced pressure
10. customThe residue was recrystallised from ethyl acetate/hexane

ORD record

ord-8c5b31836f3946dd9d1ae1d9ff0a4862

Source dataset

uspto-grants-2005_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06949576B2