Chemical Properties
CLEAR SLIGHTLY BROWNISH LIQUID
Uses
2-Thiophenebutanoic Acid is used to prepare cell-penetrating peptide α-keto-amide calpain inhibitors as potential treatment for muscular dystrophy. it is also used to prepare isochroman carboxylic acid derivatives as potential anti-diabetic agents.
Definition
ChEBI: A monocarboxylic acid that is butyric acid bearing a 2-thienyl group at position 4.
Synthesis
The general procedure for the synthesis of 4-(2-thienyl)butyric acid from 3-(2-thiophenecarbonyl)propionic acid was as follows: 4-oxo-4-(thiophen-2-yl)butyric acid (2.3 g, 12.48 mmol) was dissolved in ethylene glycol (30 mL), and hydrazine hydrate (99%, 2.2 mL, 45.9 mmol) and potassium hydroxide pellets (2.37 g, 42.4 mmol). The reaction mixture was heated to 180 °C and maintained for 10 hours. After completion of the reaction, it was cooled to room temperature and the reaction mixture was diluted with water. The aqueous layer was washed with ether, acidified with 6N hydrochloric acid and extracted with ether. The organic layers were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 2% dichloromethane solution in methanol) to give 4-(thiophen-2-yl)butanoic acid (1.8 g, 85% yield). The product was confirmed by 1H NMR (300 MHz, DMSO-d6) and mass spectrometry (ESI): 1H NMR δ 12.06 (s, 1H), 7.31-7.29 (m, 1H), 6.94-6.91 (m, 1H), 6.84-6.82 (m, 1H), 2.82-2.77 (t, J=7.7 Hz, 2H), 2.27- 2.22 (t, J=7.3Hz, 2H), 1.86-1.76 (m, 2H); MS (ESI) m/z: [M+H]+ Calculated value 170.04, measured value 170.8.
References
[1] European Journal of Medicinal Chemistry, 1998, vol. 33, # 11, p. 867 - 877
[2] Patent: WO2011/88187, 2011, A1. Location in patent: Page/Page column 60-61
[3] Patent: WO2010/76188, 2010, A1. Location in patent: Page/Page column 17-19
[4] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1980, p. 1185 - 1193
[5] Archiv der Pharmazie, 1988, vol. 321, # 10, p. 735 - 738
